Monday, March 21, 2022

Onconova Therapeutics (ONTX)
Full-Year Financial Report Included Strong Pipeline Progress

Onconova Therapeutics Inc is a clinical-stage biopharmaceutical company operating in the US. It focuses on discovering and developing novel small molecule product candidates primarily to treat cancer. The company has created a library of targeted agents designed to work against cellular pathways important to cancer cells. Its product candidates are Single-agent IV rigosertib, Oral rigosertib + azacitidine, IV Briciclib, Recilisib, and ON 123300. The key product candidate Rigosertib is a small molecule which blocks cellular signaling by targeting RAS effector pathways.

Robert LeBoyer, Vice President, Research Analyst, Life Sciences, Noble Capital Markets, Inc.

Refer to the full report for the price target, fundamental analysis, and rating.

Onconova Reported FY2021 and Updated Its Clinical Trials In Progress.  Onconova reported a loss of $16.2 million or $(0.96) per share for FY2021. Importantly, the company reiterated its development schedule for the announcement of clinical data and the start of new clinical trials. Cash on hand on December 31, 2021 was $55.1 million or $2.64 per share.

Narazaciclib Continues Patient Treatment In Its Dose Escalation Trials.  Narazaciclib is currently in two trials testing increasing doses and different administration schedules. The US trial is enrolling patients in its fourth cohort dosed at 160 mg once daily. The China trial is testing its fifth cohort at 200mg in cycles of daily dosing for three weeks followed by one week off. Data from these …

This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).

*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision. 

 

Tonix Pharmaceuticals Announces Phase 3 RALLY Study Results for TNX-102 SL 5.6 mg for the Management of Fibromyalgia

Research, News, and Market Data on Tonix Pharmaceuticals

 

As Expected Based on Interim Analysis Results Reported in July 2021, TNX-102 SL Did Not Achieve Statistical Significance Over Placebo on the Primary Endpoint of Reduction in Daily Pain in RALLY Study

Relative to the Previous Positive Phase 3 Study (RELIEF), RALLY had an Unexpected Increase in Study Participant Adverse Event-Related Discontinuations in both Drug and Placebo Groups

TNX-102 SL Generally Well Tolerated with Overall Adverse Event Profile Comparable to Prior Studies; No New Safety Signals Observed

Confirmatory Phase 3 Study RESILIENT for the Management of Fibromyalgia Planning to Enroll Participants Imminently

CHATHAM, N.J., March 21, 2022 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that, as expected based on previously reported pre-specified interim analysis results, TNX-102 SL (cyclobenzaprine HCl sublingual tablets)¹ did not achieve statistical significance on the primary endpoint of reducing fibromyalgia (FM) daily pain at Week 14 compared to placebo (p=0.115) in the Phase 3 RALLY study. RALLY was a 14-week randomized, double-blind, placebo-controlled trial of TNX-102 SL 5.6 mg, in which 514 participants with FM were randomized in a 1:1 ratio across 36 U.S. sites. All participants received TNX-102 SL 2.8 mg or placebo for the first two weeks, which was increased to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks. Tonix reported interim analysis results of RALLY in July 2021 at which time the Independent Data Monitoring Committee recommended stopping the study as it was unlikely to succeed on the primary endpoint for the planned full sample. The Company therefore stopped enrollment of new participants while continuing those enrolled at that time to completion.

TNX-102 SL is in mid-Phase 3 development for the management of fibromyalgia. In December 2020, Tonix reported positive results from the Phase 3 RELIEF study of TNX-102 SL 5.6 mg for the management of FM (primary endpoint, p=0.010). FM is a pain disorder characterized by chronic widespread pain, non-restorative sleep, fatigue, and impaired cognition. Approximately one-fourth of FM patients resort to prescription opioids for analgesia². TNX-102 SL is a centrally acting analgesic that has the potential to be a new non-addictive, non-opioid bedtime medication for the management of FM. Cyclobenzaprine, the active ingredient of TNX-102 SL, has no recognized potential for addiction.

“The positive outcome of the earlier RELIEF study stands in contrast to the missed primary endpoint in RALLY,” said Dr. Gregory Sullivan, M.D., Chief Medical Officer of Tonix. “We believe the difference between these study results may be driven in large part by a 79% increase in adverse event-related participant discontinuations in the drug treatment group in RALLY as compared to RELIEF. Similarly, a 77% increase of adverse event-related participant discontinuations was observed in the placebo group in RALLY as compared to RELIEF.” (Table 1)

Table 1. Increases in AE-Related Discontinuations in RALLY Compared with RELIEF in Both Placebo and TNX-102 SL Groups
	RALLY (F306)		RELIEF (F304)		RALLY (F306)		RELIEF (F304)
	Placebo				TNX-102 SL
Patients with at least one TEAE leading to early discontinuation	6.2	%	3.5	%	15.2	%	8.5	%
Ratio of patients with at least one TEAE leading to early discontinuation in F306 to F304 (F306/F304)	1.77				1.79

TEAE = treatment-emergent adverse event

The missing data for the primary and secondary endpoints were imputed by a method called ‘multiple imputation’ (MI), and discontinuations due to adverse events can negatively impact the statistical outcome when using this approach. Since 2010, The U.S. Food and Drug Administration (FDA) has generally required MI be used to account for missing data in efficacy analyses. Table 2 illustrates how the higher discontinuation rates due to adverse events attenuate the p-values of RALLY using the MI approach.

Table 2: Comparisons of Analytic Methods on Primary and Secondary Endpoints at Week 14 Between the RALLY and RELIEF Phase 3 Studies of TNX-102 SL 5.6 mg in Fibromyalgia

	RALLY (F306)
	MMRM+MI*		MMRM**
Endpoints	LSMD (SE)	p-value	LSMD (SE)	p-value
Pain by Diary	-0.2 (0.16)	0.115#	-0.4 (0.16)	0.014
FIQR Symptom domain	-1.9 (1.52)	0.216	-3.4 (1.55)	0.030
FIQR Function domain	-0.4 (1.46)	0.797	-1.6 (1.48)	0.266
PROMIS Sleep Disturbance	-2.3 (0.80)	0.004	-3.3 (0.73)	<0.001
PROMIS Fatigue	-1.2 (0.74)	0.101	-2.0 (0.73)	0.007
Sleep Quality by Diary	-0.3 (0.16)	0.094	-0.4 (0.16)	0.008
	RELIEF (F304)
	MMRM+MI*		MMRM**
Endpoints	LSMD (SE)	p-value	LSMD (SE)	p-value
Pain by Diary	-0.4 (0.16)	0.010#	-0.5 (0.16)	0.004
FIQR Symptom domain	-4.3 (1.60)	0.007	-5.6 (1.60)	<0.001
FIQR Function domain	-4.4 (1.69)	0.009	-5.2 (1.63)	0.001
PROMIS Sleep Disturbance	-2.9 (0.82)	<0.001	-3.3 (0.82)	<0.001
PROMIS Fatigue	-1.8 (0.76)	0.018	-2.1 (0.79)	0.007
Sleep Quality by Diary	-0.6 (0.17)	<0.001	-0.7 (0.17)	<0.001

FIQR = Fibromyalgia Impact Questionnaire-Revised; LSMD = least squares mean difference
(between TNX-102 SL and placebo); MMRM = mixed model repeated measures; MI = multiple imputation;
PROMIS = Patient-Reported Outcomes Measurement Information System; SE = standard error
* MMRM with MI was the pre-specified primary analysis
**MMRM without MI was a pre-specified analysis
^# Primary efficacy endpoint: change from baseline in the weekly average of daily diary pain severity numerical rating scale scores

Dr. Sullivan continued, “When the data are analyzed without MI, the results of RALLY appear consistent with the previous RELIEF study. The mixed model repeated measures (MMRM) results without MI method are presented to illustrate the impact of the increased discontinuations on the results when using MI as the primary analytic approach. At this time, the anticipated analytic approach for the upcoming Phase 3 RESILIENT study is MMRM with MI.”

“Without knowing the precise reasons, we postulate the increased rate of adverse event-related discontinuations may be related to conducting the study during the peak phase of the COVID-19 pandemic in the U.S., during which time vaccines were being rolled out,” said Dr. Seth Lederman, M.D., Chief Executive Officer of Tonix. “Since the pandemic phase of COVID-19 appears to be transitioning to an endemic phase, we believe that starting the new RESILIENT Phase 3 study imminently is justified based on the expectation that rates of adverse event-related discontinuations will return toward the levels of RELIEF and our PTSD studies. We are grateful to the individuals who participated in the RALLY study, and to their families, particularly because of the many challenges presented by different phases of the COVID-19 pandemic.”

“Tonix remains dedicated to improving the lives of the millions suffering from fibromyalgia,” Dr. Lederman continued. “FM is a complex syndrome, and while TNX-102 SL at 5.6 mg missed the primary endpoint in RALLY, it continued to show strong activity on sleep disturbance (p=0.004) and on the Patient Global Impression of Change (PGIC; p=0.038), which is a patient-reported assessment of overall improvement during the trial. These findings and our general understanding of TNX-102 SL tolerability encourage us to move forward with our plans to initiate our new F307 RESILIENT Phase 3 study for fibromyalgia in the first half of 2022.”

¹TNX-102 SL is an investigational new drug and has not been approved for any indication.

²Sarmento, CVM, et al. “Opioid prescription patterns among patients with fibromyalgia.” J Opioid Manag.  2019;15(6):469-477.  doi: 10.5055/jom.2019.0537. PMID: 31850508; https://pubmed.ncbi.nlm.nih.gov/31850508/

EFFICACY RESULTS OF THE PHASE 3 RALLY STUDY

The RALLY study missed statistical significance on the primary efficacy endpoint: change from baseline to Week 14 in the weekly average of daily diary pain severity numerical rating scale (NRS) scores for TNX-102 SL 5.6 mg (LS mean [SE]: -1.6 [0.11] units) versus placebo (-1.3 [0.11] units), analyzed by mixed model repeated measures with multiple imputation (MMRM+MI) (LS mean difference [SE]: -0.2 [0.16] units, p=0.115, Table 2).

Key secondary endpoint results
The responder analysis of PGIC was nominally significant (Pearson’s Chi-square test; difference in proportions [95% CI]: 8.0% [0.5%, 15.5%]; p=0.038), with a greater proportion of responders (rating of “very much improved” or “much improved” at Week 14) receiving TNX-102 SL (29.7%) compared to placebo (21.7%).

Consistent with the proposed mechanism that TNX-102 SL acts in FM through improving sleep quality, TNX-102 SL achieved nominal significance on the PROMIS Sleep Disturbance measure (LS mean difference [SE]: -2.3 [0.80] units; p=0.004). As shown in Table 2, other key secondary endpoints did not achieve nominal significance, including the Fibromyalgia Impact Questionnaire–Revised (FIQR) Symptom and Function domains, the PROMIS Fatigue instrument, and the daily sleep quality diary.

SAFETY RESULTS OF THE PHASE 3 RALLY STUDY

In the RALLY study, TNX-102 SL 5.6 mg was well tolerated. There were no new safety signals observed. Among participants randomized to the drug treatment and placebo groups, 73.8% and 81.4%, respectively, completed the 14-week dosing period. As expected, based on prior TNX-102 SL studies, oral administration site reactions were higher in the drug treatment group, including rates of tongue/mouth numbness, pain/discomfort of tongue/mouth, and product taste abnormal (typically a transient bitter aftertaste) (Table 3). Tongue/mouth numbness or tingling and product aftertaste were local effects nearly always temporally related to dose administration and transiently expressed (<60 minutes) in most occurrences. Adverse events resulted in premature study discontinuation in 15.2% of those who received TNX-102 SL compared with 6.2% of placebo recipients. Approximately 95% of adverse events in both the drug treatment and placebo groups were rated as mild or moderate. There were a total of six serious adverse events (SAEs) in the drug treatment group, none of which were deemed related to investigational product.

Table 3. Treatment-Emergent Adverse Events at Rate of 3% or Greater in TNX-102 SL Group in RALLY

Oral Cavity or Systemic Adverse Events	TNX-102 SL (N=256)	Placebo (N=258)
Preferred Term
Oral Cavity Adverse Events
Hypoaesthesia oral	72 (28.1%)	2 (0.8%)
Product taste abnormal	26 (10.2%)	2 (0.8%)
Oral discomfort	23 (9.0%)	2 (0.8%)
Tongue discomfort	16 (6.3%)	2 (0.8%)
Paraesthesia oral	11 (4.3%)	0 (0.0%)
Dry mouth	10 (3.9%)	6 (2.3%)
Oral pain	8 (3.1%)	0 (0.0%)
Systemic Adverse Events
Headache	12 (4.7%)	11 (4.3%)
Somnolence	12 (4.7%)	2 (0.8%)
Sedation	10 (3.9%)	2 (0.8%)
Fatigue	8 (3.1%)	1 (0.4%)
COVID-19	8 (3.1%)	7 (2.7%)

About Fibromyalgia

Fibromyalgia is a chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system. Fibromyalgia afflicts an estimated 6-12 million adults in the U.S., approximately 90% of whom are women. Symptoms of fibromyalgia include chronic widespread pain, nonrestorative sleep, fatigue, and morning stiffness. Other associated symptoms include cognitive dysfunction and mood disturbances, including anxiety and depression. Individuals suffering from fibromyalgia struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products.

About TNX-102 SL

TNX-102 SL is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities at the serotonin-2A, alpha-1 adrenergic, histamine-H1, and muscarinic-M1 receptors, TNX-102 SL is in development as a daily bedtime treatment for fibromyalgia, PTSD, Long COVID (PASC), alcohol use disorder and agitation in Alzheimer’s disease. The United States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408 in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic™ protective eutectic and Angstro-Technology™ formulation claimed in the patent are important elements of Tonix’s proprietary TNX-102 SL composition. These patents are expected to provide TNX-102 SL, upon NDA approval, with U.S. market exclusivity until 2034/2035.

About the Phase 3 RALLY Study

The RALLY study was a double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of TNX-102 SL (cyclobenzaprine HCl sublingual tablets). The two-arm trial enrolled 514 participants across 36 U.S. sites. For the first two weeks of treatment, there was a run-in period in which participants started on TNX-102 SL 2.8 mg (1 tablet) or placebo. After the first two weeks, all participants had the dose increased to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for 12 weeks. The primary endpoint was daily diary pain severity score change (TNX-102 SL 5.6 mg vs. placebo) from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation. An interim analysis by an Independent Data Monitoring Committee was conducted on the primary endpoint based on the first 50% of enrolled participants.

The first interim cohort of the study was enrolled between September 2020 and March 2021, which included the periods of the second and third waves of the COVID-19 pandemic in US. The post-interim cohort was enrolled between third week of March and last week of July 2021. At the time of the interim analysis in July 2021, there were 125 participants still active in the study, who all completed their participation by 1 November 2021.

About Tonix Pharmaceuticals Holding Corp.

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics and diagnostics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of immunology, central nervous system (CNS) and infectious disease product candidates. The Company’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL², (cyclobenzaprine HCl sublingual tablets), is a small molecule drug in mid-Phase 3 development for the management of fibromyalgia, with a new Phase 3 study expected to start in the first half of 2022. TNX-102 SL is also being developed to treat Long COVID, a chronic post-COVID-19 condition. Tonix expects to initiate a Phase 2 study in Long COVID in the first half of 2022. TNX-1300³ is a biologic designed to treat cocaine intoxication that is expected to start a Phase 2 trial in the first half of 2022. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer. Tonix’s lead immunology candidate, TNX-1500¹, is a humanized monoclonal antibody targeting CD40 ligand being developed for the prevention of allograft rejection and the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to start in the second half of 2022. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox, next-generation vaccines to prevent COVID-19 and an antiviral to treat COVID-19. Tonix’s lead vaccine program is TNX-801 (live horsepox virus for percutaneous administration) for preventing smallpox and monkeypox⁴. Horsepox is also the basis for Tonix’s recombinant pox vaccine (RPV) platform. Tonix’s lead vaccine candidates for COVID-19, TNX-1840 and TNX-1850⁵, are live virus vaccines in development based on the RPV platform. Finally, TNX-3500⁶ (sangivamycin, i.v. solution) is a small molecule antiviral drug to treat acute COVID-19 and is in the pre-IND stage of development.

¹TNX-1500 is an investigational new biologic at the pre-IND stage of development and has not been approved for any indication.

²TNX-102 SL is an investigational new drug and has not been approved for any indication.

³TNX-1300 is an investigational new biologic and has not been approved for any indication.

⁴TNX-801 is an investigational new biologic at the pre-IND stage of development and has not been approved for any indication.

⁵TNX-1840 and TNX-1850 are investigational new biologics at the pre-IND stage of development and have not been approved for any indication. TNX-1840 and TNX-1850 are designed to express the spike protein of SARS-CoV-2 from omicron and BA.2 variants, respectively, based on the experience from TNX-1800, which expresses the spike protein from the ancestral Wuhan strain.

⁶TNX-3500 is an investigational new drug at the pre-IND stage of development and has not been approved for any indication.

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward-Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the development of TNX-102 SL; the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 799-8599

Olipriya Das, Ph.D. (media)
Russo Partners
olipriya.das@russopartnersllc.com
(646) 942-5588

Peter Vozzo (investors)
ICR Westwicke
peter.vozzo@westwicke.com
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

 

Lineage Announces Pipeline Expansion To Include Auditory Neuronal Cell Therapy For Treatment Of Hearing Loss

Research, News, and Market Data on Lineage Cell Therapeutics

 

• Expansion of Pipeline Into a Third Neuronal Cell Type Builds on Existing Capabilities
• Intellectual Property Has Been Filed Covering Composition and Methods for Generating Auditory Neuronal Progenitors
• Hearing Loss Afflicts More Than 5% of the Population; More Than 430 Million People

CARLSBAD, Calif.–(BUSINESS WIRE)–Mar. 21, 2022– 

Lineage Cell Therapeutics, Inc.
 (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, today announced that the Company is expanding its novel cell therapy pipeline to include a new investigational product candidate, an auditory neuronal cell transplant for the treatment of hearing loss, with an initial focus on the treatment of auditory neuropathy spectrum disorders. To support this new therapeutic effort, Lineage has filed for intellectual property covering the composition and methods for generating auditory neuronal progenitors which may be capable of functioning as sensory neurons and the connecting neuronal ganglion cells of the ear, and to methods of treatment that employ these cells for the potential treatment of auditory neuropathy. According to the 
World Health Organization, hearing loss currently afflicts over 5% of the world’s population, or more than 430 million people, and by 2050 it is estimated that one in every ten people, or more than 700 million people, will have disabling hearing loss.

“Hearing loss is a major sensory deficit which affects an enormous number of individuals worldwide, yet current approaches leave much room for improvement. I am pleased to be advising Lineage and providing insights and experience in the launch of this new endeavor and working toward developing cell-based solutions for this condition,” stated 
Stefan Heller, Ph.D., Edward C. and  Amy H. Sewall Professor, 
Stanford University School of Medicine, 
Department of Otolaryngology – Head & 
Neck Surgery and Institute for Stem Cell Biology and Regenerative Medicine ISCBRM.

“We are excited to announce this new, internally-developed initiative for Lineage, and to do it so quickly following the partnership we announced with Roche and 
Genentech for our lead program, OpRegen^®, in a deal worth up to 
$670M USD,” added  Brian Culley, Lineage CEO. “Many patients with sensorineural hearing loss are poorly addressed, cannot benefit from cochlear implants, and/or have no FDA-approved treatment options. Similar to OpRegen, which has demonstrated to be able to replace and restore retinal pigment epithelium cells in patients with vision loss, and OPC1, which similarly replaces oligodendrocytes for the treatment of spinal cord injury, replacing auditory neurons or augmenting an existing but damaged auditory neuron population may provide a benefit beyond the reach of alternate approaches such as prostheses. We believe auditory neuronal transplants represent a unique opportunity to leverage our knowhow and capabilities in cellular differentiation into a fourth indication with a large unmet need. In addition to the speed with which the team created this new program from our internal technology, we have done so with a modest investment of capital so far, because we were able to take advantage of our established manufacturing infrastructure and broad knowhow in the expansion and differentiation of pluripotent cells. This is another example of the efficiency and versatility of our technology platform, which is gaining broader awareness, and which offers us a favorable competitive position in the emerging fields of regenerative medicine and anti-aging technologies.”

Auditory neuropathy is a hearing disorder in which the inner ear successfully detects sound but has a problem with sending signals from the ear to the brain. Current state of the art medical knowledge suggests that auditory neuropathies play a substantial role in hearing impairments and deafness. Hearing depends on a series of complex steps that change sound waves in the air into electrical signals. The auditory nerve then carries these signals to the brain. Outer hair cells help amplify sound vibrations entering the inner ear from the middle ear. When hearing is working normally, the inner hair cells convert these vibrations into electrical signals that travel as nerve impulses to the brain, where the brain interprets the impulses as sound. Auditory neuropathy can be caused by a number of factors including: (i) damage to the auditory neurons that transmit sound information from the inner hair cells – specialized sensory cells in the inner ear – to the brain; (ii) damage to the inner hair cells themselves; (iii) inherited genes with mutations or suffering damage to the auditory system, either of which may result in faulty connections between the inner hair cells and the auditory nerve, which leads from the inner ear to the brain; or (iv) damage to the auditory nerve itself. Researchers are still seeking effective treatments for those affected with auditory neuropathy.

About Lineage Cell Therapeutics, Inc.

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineage’s programs are based on its robust proprietary cell-based therapy platform and associated in-house development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed to either replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineage’s clinical programs are in markets with billion dollar opportunities and include four allogeneic (“off-the-shelf”) product candidates: (i) OpRegen, a retinal pigment epithelium transplant therapy in Phase 1/2a development for the treatment of dry age-related macular degeneration, which is now being developed under a worldwide collaboration with Roche and 
Genentech, a member of the Roche Group; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase 1/2a development for the treatment of acute spinal cord injuries; (iii) VAC2, a dendritic cell therapy produced from Lineage’s VAC technology platform for immuno-oncology and infectious disease, currently in Phase 1 clinical development for the treatment of non-small cell lung cancer and (iv) ANP1, an auditory neuronal progenitor cell therapy for the potential treatment of auditory neuropathy. For more information, please visit www.lineagecell.com or follow the Company on Twitter @LineageCell.

Forward-Looking Statements

Lineage cautions you that all statements, other than statements of historical facts, contained in this press release, are forward-looking statements. Forward-looking statements, in some cases, can be identified by terms such as “believe,” “aim,” “may,” “will,” “estimate,” “continue,” “anticipate,” “design,” “intend,” “expect,” “could,” “can,” “plan,” “potential,” “predict,” “seek,” “should,” “would,” “contemplate,” “project,” “target,” “tend to,” or the negative version of these words and similar expressions. Such statements include, but are not limited to, statements relating to the collaboration and license agreement with Roche and 
Genentech and activities expected to occur thereunder, the upfront, milestone and royalty consideration payable to Lineage and Lineage’s planned use of proceeds therefrom; the potential benefits of treatment with OpRegen, the potential success of other existing partnerships and collaborations, the broad potential for Lineage’s regenerative medicine platform and Lineage’s ability to expand the same; Lineage’s plans to advance its spinal cord injury, oncology and auditory neuron programs and announce new disease settings where it plans to deploy its technology; the projected timing of milestones of future studies, including their initiation and completion, the projected timing of interactions with the FDA to discuss product designation, manufacturing plans and improvements, and later-stage clinical development; the potential opportunities for the establishment or expansion of strategic partnerships and collaborations and the timing thereof, and the potential for Lineage’s investigational allogeneic cell therapies to generate clinical outcomes beyond the reach of traditional methods and provide safe and effective treatment for multiple, diverse serious or life threatening conditions. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Lineage’s actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in this press release, including, but not limited to, the risk that competing alternative therapies may adversely impact the commercial potential of OpRegen, which could materially adversely affect the milestone and royalty payments payable to Lineage under the collaboration and license agreement, the risk that Roche and 
Genentech may not be successful in completing further clinical trials for OpRegen and/or obtaining regulatory approval for OpRegen in any particular jurisdiction, the risk that Lineage might not succeed in developing products and technologies that are useful in medicine and demonstrate the requisite safety and efficacy to achieve regulatory approval in accordance with its projected timing, or at all; the risk that Lineage may not be able to manufacture sufficient clinical and, if approved, commercial quantities of its product candidates in accordance with current good manufacturing practice; the risks related to Lineage’s dependence on other third parties, and Lineage’s ability to establish and maintain its collaborations with these third parties; the risk that government-imposed bans or restrictions and religious, moral, and ethical concerns about the use of hES cells could prevent Lineage or its partners from developing and successfully marketing its stem cell product candidates; the risk that Lineage’s intellectual property may be insufficient to protect its products; the risk that the COVID-19 pandemic or geopolitical events may directly or indirectly cause significant delays in and substantially increase the cost of development of Lineage’s product candidates, as well as heighten other risks and uncertainties related to Lineage’s business and operations; risks and uncertainties inherent in Lineage’s business and other risks discussed in Lineage’s filings with the 
Securities and Exchange Commission (SEC). Lineage’s forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. Further information regarding these and other risks is included under the heading “Risk Factors” in Lineage’s periodic reports with the 
SEC, including Lineage’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the 
SEC and its other reports, which are available from the SEC’s website. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Lineage undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Lineage Cell Therapeutics, Inc. IR
Ioana C. Hone
(ir@lineagecell.com)
(442) 287-8963

Solebury Trout IR
Mike Biega
(Mbiega@soleburytrout.com)
(617) 221-9660

Russo Partners – Media Relations
Nic Johnson or  David Schull
Nic.johnson@russopartnersllc.com
David.schull@russopartnersllc.com
(212) 845-4242

Source: 
Lineage Cell Therapeutics, Inc.

  Image: Aurolean Adoue (Flickr)

AI Maps Psychedelic ‘Trip’ experiences to Regions of the Brain – Opening New Route to Psychiatric Treatments

 

For the past several decades, psychedelics have been widely stigmatized as dangerous illegal drugs. But a recent surge of academic research into their use to treat psychiatric conditions is spurring a recent shift in public opinion.

Psychedelics are psychotropic drugs: substances that affect your mental state. Other types of psychotropics include antidepressants and anti-anxiety medications. Psychedelics and other types of hallucinogens, however, are unique in their ability to temporarily induce intense hallucinations, emotions and disruptions of self-awareness.

Researchers looking into the therapeutic potential of these effects have found that psychedelics can dramatically reduce symptoms of depression and anxiety, PTSD, substance abuse and other psychiatric conditions. The intense experiences, or “trips,” that psychedelics induce are thought to create a temporary window of cognitive flexibility that allows patients to gain access to elusive parts of their psyches and forge better coping skills and thought patterns.

Precisely how psychedelics create these effects, however, is still unclear. So as researchers in psychiatry and machine learning, we were interested in figuring out how these drugs affect the brain. With artificial intelligence, we were able to map people’s subjective experiences while using psychedelics to specific regions of the brain, down to the molecular level.

Psilocybin, a psychoactive compound found in some mushrooms, has been the focus of many studies for its potential therapeutic qualities. 24K-Production/iStock via Getty Images

 

Mapping ‘Trips’ in the Brain

Every psychedelic functions differently in the body, and each of the subjective experiences these drugs create have different therapeutic effects. Mystical type experiences, or feelings of unity and oneness with the world, for example, are associated with decreases in depression and anxiety. Knowing how each psychedelic creates these specific effects in the body can help clinicians optimize their therapeutic use.

To better understand how these subjective effects manifest in the brain, we analyzed over 6,000 written testimonials of hallucinogenic experiences from Erowid Center, an organization that collects and provides information about psychoactive substances. We transformed these testimonials into what’s called a bag-of-words model, which breaks down a given text into individual words and counts how many times each word appears. We then paired the most commonly used words linked to each psychedelic with receptors in the brain that are known to bind to each drug. After using an algorithm to extract the most common subjective experiences associated with these word-receptor pairs, we mapped these experiences onto different brain regions by matching them to the types of receptors present in each area.

We found both new links and patterns that confirm what’s known in the research literature. For example, changes in sensory perception were associated with a serotonin receptor in the visual cortex of the brain, which binds to a molecule that helps regulate mood and memory. Feelings of transcendence were connected to dopamine and opioid receptors in the salience network, a collection of brain regions involved in managing sensory and emotional input. Auditory hallucinations were linked to a number of receptors spread throughout the auditory cortex.

Our findings also align with the leading hypothesis that psychedelics temporarily reduce top-down executive function, or cognitive processes involved in inhibition, attention and memory, among others, while amplifying brain regions involved in sensory experience.

 

Why it Matters

The U.S. is going through a profound mental health crisis that has been exacerbated by the COVID-19 pandemic. Yet there have been no truly new psychiatric drug treatments since Prozac and other selective serotonin reuptake inhibitors, the most common type of antidepressants, of the 1980s.

Our study shows that it’s possible to map the diverse and wildly subjective psychedelic experiences to specific regions in the brain. These insights may lead to new ways to combine existing or yet to be discovered compounds to produce desired treatment effects for a range of psychiatric conditions.

Pychiatrist Stanislav Grof famously proposed, “[P]sychedelics, used responsibly and with proper caution, would be for psychiatry what the microscope is to the study of biology and medicine or the telescope for astronomy.” As psychedelics and other hallucinogens become more commonly used clinically and culturally, we believe more research will further illuminate the biological basis of the experiences they invoke and help realize their potential.

 

This article was republished with permission from The Conversation, a news site dedicated to sharing ideas from academic experts. It represents the research-based findings and thoughts of Galen Ballentine, Resident in Psychiatry, SUNY Downstate Health Sciences University and Sam Friedman, Machine Learning Scientist at the Broad Institute of MIT &, Harvard University.

 

Suggested Reading

Prominent Study Suggests Magic Mushroom Ingredient on Depression has Long-Term Benefit

Stem Cell Science and The New Age of Therapeutic Discovery

Immune Response to Gene Therapy and How CRISPR Works to Combat It

A Quick Look at 8 Small Caps in the Growing Psychedelics Space

 

Stay up to date. Follow us:

  Image: Aurolean Adoue (Flickr)

AI Maps Psychedelic ‘Trip’ experiences to Regions of the Brain – Opening New Route to Psychiatric Treatments

 

For the past several decades, psychedelics have been widely stigmatized as dangerous illegal drugs. But a recent surge of academic research into their use to treat psychiatric conditions is spurring a recent shift in public opinion.

Psychedelics are psychotropic drugs: substances that affect your mental state. Other types of psychotropics include antidepressants and anti-anxiety medications. Psychedelics and other types of hallucinogens, however, are unique in their ability to temporarily induce intense hallucinations, emotions and disruptions of self-awareness.

Researchers looking into the therapeutic potential of these effects have found that psychedelics can dramatically reduce symptoms of depression and anxiety, PTSD, substance abuse and other psychiatric conditions. The intense experiences, or “trips,” that psychedelics induce are thought to create a temporary window of cognitive flexibility that allows patients to gain access to elusive parts of their psyches and forge better coping skills and thought patterns.

Precisely how psychedelics create these effects, however, is still unclear. So as researchers in psychiatry and machine learning, we were interested in figuring out how these drugs affect the brain. With artificial intelligence, we were able to map people’s subjective experiences while using psychedelics to specific regions of the brain, down to the molecular level.

Psilocybin, a psychoactive compound found in some mushrooms, has been the focus of many studies for its potential therapeutic qualities. 24K-Production/iStock via Getty Images

 

Mapping ‘Trips’ in the Brain

Every psychedelic functions differently in the body, and each of the subjective experiences these drugs create have different therapeutic effects. Mystical type experiences, or feelings of unity and oneness with the world, for example, are associated with decreases in depression and anxiety. Knowing how each psychedelic creates these specific effects in the body can help clinicians optimize their therapeutic use.

To better understand how these subjective effects manifest in the brain, we analyzed over 6,000 written testimonials of hallucinogenic experiences from Erowid Center, an organization that collects and provides information about psychoactive substances. We transformed these testimonials into what’s called a bag-of-words model, which breaks down a given text into individual words and counts how many times each word appears. We then paired the most commonly used words linked to each psychedelic with receptors in the brain that are known to bind to each drug. After using an algorithm to extract the most common subjective experiences associated with these word-receptor pairs, we mapped these experiences onto different brain regions by matching them to the types of receptors present in each area.

We found both new links and patterns that confirm what’s known in the research literature. For example, changes in sensory perception were associated with a serotonin receptor in the visual cortex of the brain, which binds to a molecule that helps regulate mood and memory. Feelings of transcendence were connected to dopamine and opioid receptors in the salience network, a collection of brain regions involved in managing sensory and emotional input. Auditory hallucinations were linked to a number of receptors spread throughout the auditory cortex.

Our findings also align with the leading hypothesis that psychedelics temporarily reduce top-down executive function, or cognitive processes involved in inhibition, attention and memory, among others, while amplifying brain regions involved in sensory experience.

 

Why it Matters

The U.S. is going through a profound mental health crisis that has been exacerbated by the COVID-19 pandemic. Yet there have been no truly new psychiatric drug treatments since Prozac and other selective serotonin reuptake inhibitors, the most common type of antidepressants, of the 1980s.

Our study shows that it’s possible to map the diverse and wildly subjective psychedelic experiences to specific regions in the brain. These insights may lead to new ways to combine existing or yet to be discovered compounds to produce desired treatment effects for a range of psychiatric conditions.

Pychiatrist Stanislav Grof famously proposed, “[P]sychedelics, used responsibly and with proper caution, would be for psychiatry what the microscope is to the study of biology and medicine or the telescope for astronomy.” As psychedelics and other hallucinogens become more commonly used clinically and culturally, we believe more research will further illuminate the biological basis of the experiences they invoke and help realize their potential.

 

This article was republished with permission from The Conversation, a news site dedicated to sharing ideas from academic experts. It represents the research-based findings and thoughts of Galen Ballentine, Resident in Psychiatry, SUNY Downstate Health Sciences University and Sam Friedman, Machine Learning Scientist at the Broad Institute of MIT &, Harvard University.

 

Suggested Reading

Prominent Study Suggests Magic Mushroom Ingredient on Depression has Long-Term Benefit

Stem Cell Science and The New Age of Therapeutic Discovery

Immune Response to Gene Therapy and How CRISPR Works to Combat It

A Quick Look at 8 Small Caps in the Growing Psychedelics Space

 

Stay up to date. Follow us:

 

Lineage Announces Pipeline Expansion To Include Auditory Neuronal Cell Therapy For Treatment Of Hearing Loss

Research, News, and Market Data on Lineage Cell Therapeutics

 

• Expansion of Pipeline Into a Third Neuronal Cell Type Builds on Existing Capabilities
• Intellectual Property Has Been Filed Covering Composition and Methods for Generating Auditory Neuronal Progenitors
• Hearing Loss Afflicts More Than 5% of the Population; More Than 430 Million People

CARLSBAD, Calif.–(BUSINESS WIRE)–Mar. 21, 2022– 

Lineage Cell Therapeutics, Inc.
 (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, today announced that the Company is expanding its novel cell therapy pipeline to include a new investigational product candidate, an auditory neuronal cell transplant for the treatment of hearing loss, with an initial focus on the treatment of auditory neuropathy spectrum disorders. To support this new therapeutic effort, Lineage has filed for intellectual property covering the composition and methods for generating auditory neuronal progenitors which may be capable of functioning as sensory neurons and the connecting neuronal ganglion cells of the ear, and to methods of treatment that employ these cells for the potential treatment of auditory neuropathy. According to the 
World Health Organization, hearing loss currently afflicts over 5% of the world’s population, or more than 430 million people, and by 2050 it is estimated that one in every ten people, or more than 700 million people, will have disabling hearing loss.

“Hearing loss is a major sensory deficit which affects an enormous number of individuals worldwide, yet current approaches leave much room for improvement. I am pleased to be advising Lineage and providing insights and experience in the launch of this new endeavor and working toward developing cell-based solutions for this condition,” stated 
Stefan Heller, Ph.D., Edward C. and  Amy H. Sewall Professor, 
Stanford University School of Medicine, 
Department of Otolaryngology – Head & 
Neck Surgery and Institute for Stem Cell Biology and Regenerative Medicine ISCBRM.

“We are excited to announce this new, internally-developed initiative for Lineage, and to do it so quickly following the partnership we announced with Roche and 
Genentech for our lead program, OpRegen^®, in a deal worth up to 
$670M USD,” added  Brian Culley, Lineage CEO. “Many patients with sensorineural hearing loss are poorly addressed, cannot benefit from cochlear implants, and/or have no FDA-approved treatment options. Similar to OpRegen, which has demonstrated to be able to replace and restore retinal pigment epithelium cells in patients with vision loss, and OPC1, which similarly replaces oligodendrocytes for the treatment of spinal cord injury, replacing auditory neurons or augmenting an existing but damaged auditory neuron population may provide a benefit beyond the reach of alternate approaches such as prostheses. We believe auditory neuronal transplants represent a unique opportunity to leverage our knowhow and capabilities in cellular differentiation into a fourth indication with a large unmet need. In addition to the speed with which the team created this new program from our internal technology, we have done so with a modest investment of capital so far, because we were able to take advantage of our established manufacturing infrastructure and broad knowhow in the expansion and differentiation of pluripotent cells. This is another example of the efficiency and versatility of our technology platform, which is gaining broader awareness, and which offers us a favorable competitive position in the emerging fields of regenerative medicine and anti-aging technologies.”

Auditory neuropathy is a hearing disorder in which the inner ear successfully detects sound but has a problem with sending signals from the ear to the brain. Current state of the art medical knowledge suggests that auditory neuropathies play a substantial role in hearing impairments and deafness. Hearing depends on a series of complex steps that change sound waves in the air into electrical signals. The auditory nerve then carries these signals to the brain. Outer hair cells help amplify sound vibrations entering the inner ear from the middle ear. When hearing is working normally, the inner hair cells convert these vibrations into electrical signals that travel as nerve impulses to the brain, where the brain interprets the impulses as sound. Auditory neuropathy can be caused by a number of factors including: (i) damage to the auditory neurons that transmit sound information from the inner hair cells – specialized sensory cells in the inner ear – to the brain; (ii) damage to the inner hair cells themselves; (iii) inherited genes with mutations or suffering damage to the auditory system, either of which may result in faulty connections between the inner hair cells and the auditory nerve, which leads from the inner ear to the brain; or (iv) damage to the auditory nerve itself. Researchers are still seeking effective treatments for those affected with auditory neuropathy.

About Lineage Cell Therapeutics, Inc.

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineage’s programs are based on its robust proprietary cell-based therapy platform and associated in-house development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed to either replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineage’s clinical programs are in markets with billion dollar opportunities and include four allogeneic (“off-the-shelf”) product candidates: (i) OpRegen, a retinal pigment epithelium transplant therapy in Phase 1/2a development for the treatment of dry age-related macular degeneration, which is now being developed under a worldwide collaboration with Roche and 
Genentech, a member of the Roche Group; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase 1/2a development for the treatment of acute spinal cord injuries; (iii) VAC2, a dendritic cell therapy produced from Lineage’s VAC technology platform for immuno-oncology and infectious disease, currently in Phase 1 clinical development for the treatment of non-small cell lung cancer and (iv) ANP1, an auditory neuronal progenitor cell therapy for the potential treatment of auditory neuropathy. For more information, please visit www.lineagecell.com or follow the Company on Twitter @LineageCell.

Forward-Looking Statements

Lineage cautions you that all statements, other than statements of historical facts, contained in this press release, are forward-looking statements. Forward-looking statements, in some cases, can be identified by terms such as “believe,” “aim,” “may,” “will,” “estimate,” “continue,” “anticipate,” “design,” “intend,” “expect,” “could,” “can,” “plan,” “potential,” “predict,” “seek,” “should,” “would,” “contemplate,” “project,” “target,” “tend to,” or the negative version of these words and similar expressions. Such statements include, but are not limited to, statements relating to the collaboration and license agreement with Roche and 
Genentech and activities expected to occur thereunder, the upfront, milestone and royalty consideration payable to Lineage and Lineage’s planned use of proceeds therefrom; the potential benefits of treatment with OpRegen, the potential success of other existing partnerships and collaborations, the broad potential for Lineage’s regenerative medicine platform and Lineage’s ability to expand the same; Lineage’s plans to advance its spinal cord injury, oncology and auditory neuron programs and announce new disease settings where it plans to deploy its technology; the projected timing of milestones of future studies, including their initiation and completion, the projected timing of interactions with the FDA to discuss product designation, manufacturing plans and improvements, and later-stage clinical development; the potential opportunities for the establishment or expansion of strategic partnerships and collaborations and the timing thereof, and the potential for Lineage’s investigational allogeneic cell therapies to generate clinical outcomes beyond the reach of traditional methods and provide safe and effective treatment for multiple, diverse serious or life threatening conditions. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Lineage’s actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in this press release, including, but not limited to, the risk that competing alternative therapies may adversely impact the commercial potential of OpRegen, which could materially adversely affect the milestone and royalty payments payable to Lineage under the collaboration and license agreement, the risk that Roche and 
Genentech may not be successful in completing further clinical trials for OpRegen and/or obtaining regulatory approval for OpRegen in any particular jurisdiction, the risk that Lineage might not succeed in developing products and technologies that are useful in medicine and demonstrate the requisite safety and efficacy to achieve regulatory approval in accordance with its projected timing, or at all; the risk that Lineage may not be able to manufacture sufficient clinical and, if approved, commercial quantities of its product candidates in accordance with current good manufacturing practice; the risks related to Lineage’s dependence on other third parties, and Lineage’s ability to establish and maintain its collaborations with these third parties; the risk that government-imposed bans or restrictions and religious, moral, and ethical concerns about the use of hES cells could prevent Lineage or its partners from developing and successfully marketing its stem cell product candidates; the risk that Lineage’s intellectual property may be insufficient to protect its products; the risk that the COVID-19 pandemic or geopolitical events may directly or indirectly cause significant delays in and substantially increase the cost of development of Lineage’s product candidates, as well as heighten other risks and uncertainties related to Lineage’s business and operations; risks and uncertainties inherent in Lineage’s business and other risks discussed in Lineage’s filings with the 
Securities and Exchange Commission (SEC). Lineage’s forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. Further information regarding these and other risks is included under the heading “Risk Factors” in Lineage’s periodic reports with the 
SEC, including Lineage’s most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the 
SEC and its other reports, which are available from the SEC’s website. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Lineage undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Lineage Cell Therapeutics, Inc. IR
Ioana C. Hone
(ir@lineagecell.com)
(442) 287-8963

Solebury Trout IR
Mike Biega
(Mbiega@soleburytrout.com)
(617) 221-9660

Russo Partners – Media Relations
Nic Johnson or  David Schull
Nic.johnson@russopartnersllc.com
David.schull@russopartnersllc.com
(212) 845-4242

Source: 
Lineage Cell Therapeutics, Inc.

Tonix Pharmaceuticals Announces Phase 3 RALLY Study Results for TNX-102 SL 5.6 mg for the Management of Fibromyalgia

Research, News, and Market Data on Tonix Pharmaceuticals

 

As Expected Based on Interim Analysis Results Reported in July 2021, TNX-102 SL Did Not Achieve Statistical Significance Over Placebo on the Primary Endpoint of Reduction in Daily Pain in RALLY Study

Relative to the Previous Positive Phase 3 Study (RELIEF), RALLY had an Unexpected Increase in Study Participant Adverse Event-Related Discontinuations in both Drug and Placebo Groups

TNX-102 SL Generally Well Tolerated with Overall Adverse Event Profile Comparable to Prior Studies; No New Safety Signals Observed

Confirmatory Phase 3 Study RESILIENT for the Management of Fibromyalgia Planning to Enroll Participants Imminently

CHATHAM, N.J., March 21, 2022 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that, as expected based on previously reported pre-specified interim analysis results, TNX-102 SL (cyclobenzaprine HCl sublingual tablets)¹ did not achieve statistical significance on the primary endpoint of reducing fibromyalgia (FM) daily pain at Week 14 compared to placebo (p=0.115) in the Phase 3 RALLY study. RALLY was a 14-week randomized, double-blind, placebo-controlled trial of TNX-102 SL 5.6 mg, in which 514 participants with FM were randomized in a 1:1 ratio across 36 U.S. sites. All participants received TNX-102 SL 2.8 mg or placebo for the first two weeks, which was increased to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for the remaining 12 weeks. Tonix reported interim analysis results of RALLY in July 2021 at which time the Independent Data Monitoring Committee recommended stopping the study as it was unlikely to succeed on the primary endpoint for the planned full sample. The Company therefore stopped enrollment of new participants while continuing those enrolled at that time to completion.

TNX-102 SL is in mid-Phase 3 development for the management of fibromyalgia. In December 2020, Tonix reported positive results from the Phase 3 RELIEF study of TNX-102 SL 5.6 mg for the management of FM (primary endpoint, p=0.010). FM is a pain disorder characterized by chronic widespread pain, non-restorative sleep, fatigue, and impaired cognition. Approximately one-fourth of FM patients resort to prescription opioids for analgesia². TNX-102 SL is a centrally acting analgesic that has the potential to be a new non-addictive, non-opioid bedtime medication for the management of FM. Cyclobenzaprine, the active ingredient of TNX-102 SL, has no recognized potential for addiction.

“The positive outcome of the earlier RELIEF study stands in contrast to the missed primary endpoint in RALLY,” said Dr. Gregory Sullivan, M.D., Chief Medical Officer of Tonix. “We believe the difference between these study results may be driven in large part by a 79% increase in adverse event-related participant discontinuations in the drug treatment group in RALLY as compared to RELIEF. Similarly, a 77% increase of adverse event-related participant discontinuations was observed in the placebo group in RALLY as compared to RELIEF.” (Table 1)

Table 1. Increases in AE-Related Discontinuations in RALLY Compared with RELIEF in Both Placebo and TNX-102 SL Groups
	RALLY (F306)		RELIEF (F304)		RALLY (F306)		RELIEF (F304)
	Placebo				TNX-102 SL
Patients with at least one TEAE leading to early discontinuation	6.2	%	3.5	%	15.2	%	8.5	%
Ratio of patients with at least one TEAE leading to early discontinuation in F306 to F304 (F306/F304)	1.77				1.79

TEAE = treatment-emergent adverse event

The missing data for the primary and secondary endpoints were imputed by a method called ‘multiple imputation’ (MI), and discontinuations due to adverse events can negatively impact the statistical outcome when using this approach. Since 2010, The U.S. Food and Drug Administration (FDA) has generally required MI be used to account for missing data in efficacy analyses. Table 2 illustrates how the higher discontinuation rates due to adverse events attenuate the p-values of RALLY using the MI approach.

Table 2: Comparisons of Analytic Methods on Primary and Secondary Endpoints at Week 14 Between the RALLY and RELIEF Phase 3 Studies of TNX-102 SL 5.6 mg in Fibromyalgia

	RALLY (F306)
	MMRM+MI*		MMRM**
Endpoints	LSMD (SE)	p-value	LSMD (SE)	p-value
Pain by Diary	-0.2 (0.16)	0.115#	-0.4 (0.16)	0.014
FIQR Symptom domain	-1.9 (1.52)	0.216	-3.4 (1.55)	0.030
FIQR Function domain	-0.4 (1.46)	0.797	-1.6 (1.48)	0.266
PROMIS Sleep Disturbance	-2.3 (0.80)	0.004	-3.3 (0.73)	<0.001
PROMIS Fatigue	-1.2 (0.74)	0.101	-2.0 (0.73)	0.007
Sleep Quality by Diary	-0.3 (0.16)	0.094	-0.4 (0.16)	0.008
	RELIEF (F304)
	MMRM+MI*		MMRM**
Endpoints	LSMD (SE)	p-value	LSMD (SE)	p-value
Pain by Diary	-0.4 (0.16)	0.010#	-0.5 (0.16)	0.004
FIQR Symptom domain	-4.3 (1.60)	0.007	-5.6 (1.60)	<0.001
FIQR Function domain	-4.4 (1.69)	0.009	-5.2 (1.63)	0.001
PROMIS Sleep Disturbance	-2.9 (0.82)	<0.001	-3.3 (0.82)	<0.001
PROMIS Fatigue	-1.8 (0.76)	0.018	-2.1 (0.79)	0.007
Sleep Quality by Diary	-0.6 (0.17)	<0.001	-0.7 (0.17)	<0.001

FIQR = Fibromyalgia Impact Questionnaire-Revised; LSMD = least squares mean difference
(between TNX-102 SL and placebo); MMRM = mixed model repeated measures; MI = multiple imputation;
PROMIS = Patient-Reported Outcomes Measurement Information System; SE = standard error
* MMRM with MI was the pre-specified primary analysis
**MMRM without MI was a pre-specified analysis
^# Primary efficacy endpoint: change from baseline in the weekly average of daily diary pain severity numerical rating scale scores

Dr. Sullivan continued, “When the data are analyzed without MI, the results of RALLY appear consistent with the previous RELIEF study. The mixed model repeated measures (MMRM) results without MI method are presented to illustrate the impact of the increased discontinuations on the results when using MI as the primary analytic approach. At this time, the anticipated analytic approach for the upcoming Phase 3 RESILIENT study is MMRM with MI.”

“Without knowing the precise reasons, we postulate the increased rate of adverse event-related discontinuations may be related to conducting the study during the peak phase of the COVID-19 pandemic in the U.S., during which time vaccines were being rolled out,” said Dr. Seth Lederman, M.D., Chief Executive Officer of Tonix. “Since the pandemic phase of COVID-19 appears to be transitioning to an endemic phase, we believe that starting the new RESILIENT Phase 3 study imminently is justified based on the expectation that rates of adverse event-related discontinuations will return toward the levels of RELIEF and our PTSD studies. We are grateful to the individuals who participated in the RALLY study, and to their families, particularly because of the many challenges presented by different phases of the COVID-19 pandemic.”

“Tonix remains dedicated to improving the lives of the millions suffering from fibromyalgia,” Dr. Lederman continued. “FM is a complex syndrome, and while TNX-102 SL at 5.6 mg missed the primary endpoint in RALLY, it continued to show strong activity on sleep disturbance (p=0.004) and on the Patient Global Impression of Change (PGIC; p=0.038), which is a patient-reported assessment of overall improvement during the trial. These findings and our general understanding of TNX-102 SL tolerability encourage us to move forward with our plans to initiate our new F307 RESILIENT Phase 3 study for fibromyalgia in the first half of 2022.”

¹TNX-102 SL is an investigational new drug and has not been approved for any indication.

²Sarmento, CVM, et al. “Opioid prescription patterns among patients with fibromyalgia.” J Opioid Manag.  2019;15(6):469-477.  doi: 10.5055/jom.2019.0537. PMID: 31850508; https://pubmed.ncbi.nlm.nih.gov/31850508/

EFFICACY RESULTS OF THE PHASE 3 RALLY STUDY

The RALLY study missed statistical significance on the primary efficacy endpoint: change from baseline to Week 14 in the weekly average of daily diary pain severity numerical rating scale (NRS) scores for TNX-102 SL 5.6 mg (LS mean [SE]: -1.6 [0.11] units) versus placebo (-1.3 [0.11] units), analyzed by mixed model repeated measures with multiple imputation (MMRM+MI) (LS mean difference [SE]: -0.2 [0.16] units, p=0.115, Table 2).

Key secondary endpoint results
The responder analysis of PGIC was nominally significant (Pearson’s Chi-square test; difference in proportions [95% CI]: 8.0% [0.5%, 15.5%]; p=0.038), with a greater proportion of responders (rating of “very much improved” or “much improved” at Week 14) receiving TNX-102 SL (29.7%) compared to placebo (21.7%).

Consistent with the proposed mechanism that TNX-102 SL acts in FM through improving sleep quality, TNX-102 SL achieved nominal significance on the PROMIS Sleep Disturbance measure (LS mean difference [SE]: -2.3 [0.80] units; p=0.004). As shown in Table 2, other key secondary endpoints did not achieve nominal significance, including the Fibromyalgia Impact Questionnaire–Revised (FIQR) Symptom and Function domains, the PROMIS Fatigue instrument, and the daily sleep quality diary.

SAFETY RESULTS OF THE PHASE 3 RALLY STUDY

In the RALLY study, TNX-102 SL 5.6 mg was well tolerated. There were no new safety signals observed. Among participants randomized to the drug treatment and placebo groups, 73.8% and 81.4%, respectively, completed the 14-week dosing period. As expected, based on prior TNX-102 SL studies, oral administration site reactions were higher in the drug treatment group, including rates of tongue/mouth numbness, pain/discomfort of tongue/mouth, and product taste abnormal (typically a transient bitter aftertaste) (Table 3). Tongue/mouth numbness or tingling and product aftertaste were local effects nearly always temporally related to dose administration and transiently expressed (<60 minutes) in most occurrences. Adverse events resulted in premature study discontinuation in 15.2% of those who received TNX-102 SL compared with 6.2% of placebo recipients. Approximately 95% of adverse events in both the drug treatment and placebo groups were rated as mild or moderate. There were a total of six serious adverse events (SAEs) in the drug treatment group, none of which were deemed related to investigational product.

Table 3. Treatment-Emergent Adverse Events at Rate of 3% or Greater in TNX-102 SL Group in RALLY

Oral Cavity or Systemic Adverse Events	TNX-102 SL (N=256)	Placebo (N=258)
Preferred Term
Oral Cavity Adverse Events
Hypoaesthesia oral	72 (28.1%)	2 (0.8%)
Product taste abnormal	26 (10.2%)	2 (0.8%)
Oral discomfort	23 (9.0%)	2 (0.8%)
Tongue discomfort	16 (6.3%)	2 (0.8%)
Paraesthesia oral	11 (4.3%)	0 (0.0%)
Dry mouth	10 (3.9%)	6 (2.3%)
Oral pain	8 (3.1%)	0 (0.0%)
Systemic Adverse Events
Headache	12 (4.7%)	11 (4.3%)
Somnolence	12 (4.7%)	2 (0.8%)
Sedation	10 (3.9%)	2 (0.8%)
Fatigue	8 (3.1%)	1 (0.4%)
COVID-19	8 (3.1%)	7 (2.7%)

About Fibromyalgia

Fibromyalgia is a chronic pain disorder that is understood to result from amplified sensory and pain signaling within the central nervous system. Fibromyalgia afflicts an estimated 6-12 million adults in the U.S., approximately 90% of whom are women. Symptoms of fibromyalgia include chronic widespread pain, nonrestorative sleep, fatigue, and morning stiffness. Other associated symptoms include cognitive dysfunction and mood disturbances, including anxiety and depression. Individuals suffering from fibromyalgia struggle with their daily activities, have impaired quality of life, and frequently are disabled. Physicians and patients report common dissatisfaction with currently marketed products.

About TNX-102 SL

TNX-102 SL is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which provides rapid transmucosal absorption and reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism. As a multifunctional agent with potent binding and antagonist activities at the serotonin-2A, alpha-1 adrenergic, histamine-H1, and muscarinic-M1 receptors, TNX-102 SL is in development as a daily bedtime treatment for fibromyalgia, PTSD, Long COVID (PASC), alcohol use disorder and agitation in Alzheimer’s disease. The United States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408 in May 2017, Patent No. 9956188 in May 2018, Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic™ protective eutectic and Angstro-Technology™ formulation claimed in the patent are important elements of Tonix’s proprietary TNX-102 SL composition. These patents are expected to provide TNX-102 SL, upon NDA approval, with U.S. market exclusivity until 2034/2035.

About the Phase 3 RALLY Study

The RALLY study was a double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of TNX-102 SL (cyclobenzaprine HCl sublingual tablets). The two-arm trial enrolled 514 participants across 36 U.S. sites. For the first two weeks of treatment, there was a run-in period in which participants started on TNX-102 SL 2.8 mg (1 tablet) or placebo. After the first two weeks, all participants had the dose increased to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) or two placebo tablets for 12 weeks. The primary endpoint was daily diary pain severity score change (TNX-102 SL 5.6 mg vs. placebo) from baseline to Week 14 (using the weekly averages of the daily numerical rating scale scores), analyzed by mixed model repeated measures with multiple imputation. An interim analysis by an Independent Data Monitoring Committee was conducted on the primary endpoint based on the first 50% of enrolled participants.

The first interim cohort of the study was enrolled between September 2020 and March 2021, which included the periods of the second and third waves of the COVID-19 pandemic in US. The post-interim cohort was enrolled between third week of March and last week of July 2021. At the time of the interim analysis in July 2021, there were 125 participants still active in the study, who all completed their participation by 1 November 2021.

About Tonix Pharmaceuticals Holding Corp.

Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics and diagnostics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of immunology, central nervous system (CNS) and infectious disease product candidates. The Company’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL², (cyclobenzaprine HCl sublingual tablets), is a small molecule drug in mid-Phase 3 development for the management of fibromyalgia, with a new Phase 3 study expected to start in the first half of 2022. TNX-102 SL is also being developed to treat Long COVID, a chronic post-COVID-19 condition. Tonix expects to initiate a Phase 2 study in Long COVID in the first half of 2022. TNX-1300³ is a biologic designed to treat cocaine intoxication that is expected to start a Phase 2 trial in the first half of 2022. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer. Tonix’s lead immunology candidate, TNX-1500¹, is a humanized monoclonal antibody targeting CD40 ligand being developed for the prevention of allograft rejection and the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to start in the second half of 2022. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox, next-generation vaccines to prevent COVID-19 and an antiviral to treat COVID-19. Tonix’s lead vaccine program is TNX-801 (live horsepox virus for percutaneous administration) for preventing smallpox and monkeypox⁴. Horsepox is also the basis for Tonix’s recombinant pox vaccine (RPV) platform. Tonix’s lead vaccine candidates for COVID-19, TNX-1840 and TNX-1850⁵, are live virus vaccines in development based on the RPV platform. Finally, TNX-3500⁶ (sangivamycin, i.v. solution) is a small molecule antiviral drug to treat acute COVID-19 and is in the pre-IND stage of development.

¹TNX-1500 is an investigational new biologic at the pre-IND stage of development and has not been approved for any indication.

²TNX-102 SL is an investigational new drug and has not been approved for any indication.

³TNX-1300 is an investigational new biologic and has not been approved for any indication.

⁴TNX-801 is an investigational new biologic at the pre-IND stage of development and has not been approved for any indication.

⁵TNX-1840 and TNX-1850 are investigational new biologics at the pre-IND stage of development and have not been approved for any indication. TNX-1840 and TNX-1850 are designed to express the spike protein of SARS-CoV-2 from omicron and BA.2 variants, respectively, based on the experience from TNX-1800, which expresses the spike protein from the ancestral Wuhan strain.

⁶TNX-3500 is an investigational new drug at the pre-IND stage of development and has not been approved for any indication.

This press release and further information about Tonix can be found at www.tonixpharma.com.

Forward-Looking Statements

Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the development of TNX-102 SL; the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.

Contacts

Jessica Morris (corporate)
Tonix Pharmaceuticals
investor.relations@tonixpharma.com
(862) 799-8599

Olipriya Das, Ph.D. (media)
Russo Partners
olipriya.das@russopartnersllc.com
(646) 942-5588

Peter Vozzo (investors)
ICR Westwicke
peter.vozzo@westwicke.com
(443) 213-0505

Source: Tonix Pharmaceuticals Holding Corp.

Pandemic Mood: Much Worse than a Bad Monday

 

Peter Dizikes | MIT News
Office

The Covid-19 pandemic has been depressing, demoralizing, and stressful for people around the world. But is there any way to measure exactly how bad it has made everyone feel?

A new study led by MIT researchers attempts just that, through a massive examination of hundreds of millions social media posts in about 100 countries. The research, which analyzes the language terms used in social media, finds a pronounced drop in positive public sentiment after the pandemic set in during early 2020 — with a subsequent, incremental, halting return to prepandemic status.

To put that downturn in perspective, consider a prepandemic fact that the same kind of analysis uncovered: Typically, people express the most upbeat emotions on social media on weekends, and the most negative ones on Monday. Worldwide, the onset of the pandemic induced a negative turn in sentiment 4.7 times as large as the traditional weekend-Monday gap. Thus the early pandemic months were like a really, really bad Monday, on aggregate, globally, for social media users.

“The takeaway here is that the pandemic itself caused a huge emotional toll, four to five times the variation in sentiment observed in a normal week,” says Siqi Zheng, an MIT professor and co-author of a new paper detailing the study’s results.

The paper, “Global evidence of expressed sentiment alterations during the Covid-19 pandemic,” appears today in Nature Human Behaviour.

 

To conduct the study, the researchers examined 654 million location-identified social media posts from Twitter in about 100 countries. The posts appeared between Jan. 1, 2020, and May 31, 2020, an early phase of the global pandemic.

The researchers used natural-language processing software to evaluate the content of the social media, and examined the language of pandemic-period posts in relation to historical norms. Having previously studied the effects of pollution, extreme weather, and natural disasters on public sentiment, they found that the pandemic produced bigger changes in mood than those other circumstances.

“The reaction to the pandemic was also three to four times the change in response to extreme temperatures,” Fan observes. “The pandemic shock is even larger than the days when there is a hurricane in a region.”

The biggest drops in sentiment occurred in Australia, Spain, the United Kingdom, and Colombia. The countries least affected by the pandemic in these terms were Bahrain, Botswana, Greece, Oman, and Tunisia.

The study also revealed a potentially surprising fact about temporary lockdown policies — namely, that lockdowns did not appear to have much of an effect on the public mood.

“You can’t expect lockdowns to have the same effect on every country, and the distribution of responses is quite wide,” says Fan. “But we found the responses actually largely centered around a very small positive reaction [to lockdowns]. … It’s definitely not the overwhelmingly negative impact on people that might be expected.”

As to why people might have reacted like this, Zheng says, “On the one hand, lockdown policies might make people feel secure, and not as scared. On the other hand, in a lockdown when you cannot have social activities, it’s another emotional stress. The impact of lockdown policies perhaps runs in two directions.”

Because many factors might concurrently affect public sentiment during a lockdown, the researchers compared the mood of countries during lockdowns to those with similar characteristics that simultaneously did not enact the same policies.

The scholars also evaluated patterns of sentiment recovery during the early 2020 period, finding that some countries took as long as 29 days to erase half of the dropoff in sentiment they experienced; 18 percent of countries did not recover to their prepandemic sentiment level.

The new paper is part of the Global Sentiment project in Zheng’s Sustainable Urbanization Lab, which studies public sentiment as expressed through social media, rather than public-opinion polling.

“The traditional approach is to use surveys to measure well-being or happiness,” Zheng observes. “But a survey has smaller sample size and low frequency. This a real-time measure of people’s sentiment.”

Suggested Reading

Impact of Physical Nearness on Twitter Posts

Bond Market Understanding is Again Critical for Stock Investors

Covid-19, Scary vs. Dangerous (July 2020)

Michael Burry says COVID-19 Cure Worse than the Disease (April 2020)

 

Stay up to date. Follow us:

Pandemic Mood: Much Worse than a Bad Monday

 

Peter Dizikes | MIT News
Office

The Covid-19 pandemic has been depressing, demoralizing, and stressful for people around the world. But is there any way to measure exactly how bad it has made everyone feel?

A new study led by MIT researchers attempts just that, through a massive examination of hundreds of millions social media posts in about 100 countries. The research, which analyzes the language terms used in social media, finds a pronounced drop in positive public sentiment after the pandemic set in during early 2020 — with a subsequent, incremental, halting return to prepandemic status.

To put that downturn in perspective, consider a prepandemic fact that the same kind of analysis uncovered: Typically, people express the most upbeat emotions on social media on weekends, and the most negative ones on Monday. Worldwide, the onset of the pandemic induced a negative turn in sentiment 4.7 times as large as the traditional weekend-Monday gap. Thus the early pandemic months were like a really, really bad Monday, on aggregate, globally, for social media users.

“The takeaway here is that the pandemic itself caused a huge emotional toll, four to five times the variation in sentiment observed in a normal week,” says Siqi Zheng, an MIT professor and co-author of a new paper detailing the study’s results.

The paper, “Global evidence of expressed sentiment alterations during the Covid-19 pandemic,” appears today in Nature Human Behaviour.

 

To conduct the study, the researchers examined 654 million location-identified social media posts from Twitter in about 100 countries. The posts appeared between Jan. 1, 2020, and May 31, 2020, an early phase of the global pandemic.

The researchers used natural-language processing software to evaluate the content of the social media, and examined the language of pandemic-period posts in relation to historical norms. Having previously studied the effects of pollution, extreme weather, and natural disasters on public sentiment, they found that the pandemic produced bigger changes in mood than those other circumstances.

“The reaction to the pandemic was also three to four times the change in response to extreme temperatures,” Fan observes. “The pandemic shock is even larger than the days when there is a hurricane in a region.”

The biggest drops in sentiment occurred in Australia, Spain, the United Kingdom, and Colombia. The countries least affected by the pandemic in these terms were Bahrain, Botswana, Greece, Oman, and Tunisia.

The study also revealed a potentially surprising fact about temporary lockdown policies — namely, that lockdowns did not appear to have much of an effect on the public mood.

“You can’t expect lockdowns to have the same effect on every country, and the distribution of responses is quite wide,” says Fan. “But we found the responses actually largely centered around a very small positive reaction [to lockdowns]. … It’s definitely not the overwhelmingly negative impact on people that might be expected.”

As to why people might have reacted like this, Zheng says, “On the one hand, lockdown policies might make people feel secure, and not as scared. On the other hand, in a lockdown when you cannot have social activities, it’s another emotional stress. The impact of lockdown policies perhaps runs in two directions.”

Because many factors might concurrently affect public sentiment during a lockdown, the researchers compared the mood of countries during lockdowns to those with similar characteristics that simultaneously did not enact the same policies.

The scholars also evaluated patterns of sentiment recovery during the early 2020 period, finding that some countries took as long as 29 days to erase half of the dropoff in sentiment they experienced; 18 percent of countries did not recover to their prepandemic sentiment level.

The new paper is part of the Global Sentiment project in Zheng’s Sustainable Urbanization Lab, which studies public sentiment as expressed through social media, rather than public-opinion polling.

“The traditional approach is to use surveys to measure well-being or happiness,” Zheng observes. “But a survey has smaller sample size and low frequency. This a real-time measure of people’s sentiment.”

Suggested Reading

Impact of Physical Nearness on Twitter Posts

Bond Market Understanding is Again Critical for Stock Investors

Covid-19, Scary vs. Dangerous (July 2020)

Michael Burry says COVID-19 Cure Worse than the Disease (April 2020)

 

Stay up to date. Follow us:

Thursday, March 17, 2022

Baudax Bio (BXRX)
Fourth Quarter 2021 Reported; Major Expense Reductions Announced

Baudax Bio is a biopharmaceutical company focused on developing therapies for post-operative pain, peri-operative pain, and anesthesia. The company currently has one approved therapy in ANJESO for post-operative pain. Proprietary ANJESO (meloxicam) injection is the first and only once-daily IV analgesic. The company also has a pipeline of early-stage candidates with two novel neuromuscular blocking agents (NMBAs), a proprietary related reversal agent to their NMBAs, and Dex-IN, an intranasal formulation of dexmedetomidine (Dex) that has sedative, analgesic, and anti-anxiety properties.

Gregory Aurand, Senior Research Analyst, Healthcare Services & Medical Devices, Noble Capital Markets, Inc.

Refer to the full report for the price target, fundamental analysis, and rating.

4Q 2021 revenues reported. Yesterday, Baudax Bio released 4Q and FY 2021 results. Despite better-than-expected formulary wins, Covid related elective procedures remained muted in regions of the U.S. While solid, 4Q revenues of $.4 million, up 426%, missed our $0.55 million estimate. FY 2021 reported revenues of $1.08 million, up 119%, missed our $1.23 million estimate.

Company is reducing headcount and expenses.  The company is implementing a workplace reduction plan to curtail expenses and reduce need for capital. The plan is expected to reduce headcount 80%. The company expects approximately $4.0 million in severance and related costs to be taken by end of 2Q 2022. Cash burn will be substantially reduced in 2H 2022 and beyond …

This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).

*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision. 

 

ProMIS Neurosciences Announces Fiscal Year 2021 Results

News and Market Data on ProMIS Neurosciences

 

TORONTO, Ontario and CAMBRIDGE, Massachusetts , March 17, 2022 (GLOBE NEWSWIRE) — ProMIS Neurosciences, Inc. (TSX: PMN) (OTCQB: ARFXF) (“ProMIS” or the “Company”), a biotechnology company focused on the discovery and development of antibody therapeutics targeting misfolded proteins such as toxic oligomers, implicated in the development of neurodegenerative diseases, today announced its operational and financial results for the fiscal year ended December 31, 2021.

“2021 was an excellent year for ProMIS including strong capital formation which enabled us to advance and expand our portfolio of differentiated therapeutic product candidates such as Alzheimer’s disease (AD), ALS, and Schizophrenia,” said Gene Williams, ProMIS’ Chairman and CEO.   “We feel privileged that leading global experts continue to join our Scientific Advisory Board (SAB), accomplished executives are joining our Board of Directors, and that we have been able to supplement our strong management team, and we expect to continue those trends. We were grateful for the strong shareholder support for the resolution necessary to qualify for a potential listing on a major North American stock exchange presuming we meet the required listing standards. While biotechnology markets and specific disease sectors within biotechnology have cyclical ups and downs, we are well positioned to continue making substantive progress in our programs that could allow us to capitalize when markets rebound, as we believe they will.”

PMN310, an antibody selective for toxic oligomers in AD, is ProMIS’ lead product candidate. In the fourth quarter of 2021, the Company made significant progress on the program elements.

Producer cell line development is advancing. The genetic sequence of PMN310 has been transfected into Chinese hamster ovary (CHO) cells, the standard production cells for antibody manufacturing. We have contractually secured manufacturing slots for material to be used in Good Laboratory Practice (GLP) toxicology studies and for current Good Manufacturing Practice (cGMP) material for use in the initial clinical trials of PMN310, if allowed to proceed. In addition, we have contractually secured slots for GLP toxicology studies of various durations in nonhuman primates to support our single ascending dose/multiple ascending dose (SAD/MAD) trials. We have initiated pilot toxicology and pharmacokinetics (PK) studies to provide important information to support our GLP toxicology studies. We expect those PK studies to be completed in the second quarter of 2022. We also have secured slots for pilot and GLP tissue cross reactivity (TCR) studies, which are required for an investigational new drug (IND) application, in addition to GLP toxicology. The pilot TCR study was initiated fourth quarter of 2021 with an expected completion in second quarter 2022. Development of assays to measure drug levels in both nonhuman primate and human studies have been initiated and are expected to complete development in second quarter of 2022. Vendors have been contracted to perform these assays for our GLP studies.

In addition, in March 2022, we announced the results from a study assessing chronic systemic administration of PMN310 in a transgenic mouse model of Alzheimer’s disease, where the cognitive deficit is driven by toxic amyloid-beta oligomers. The results were positive, showing that PMN310 prevented a cognitive deficit as measured by performance in the water maze task.   

Cash expenditures for PMN310 in the six months ended December 31, 2021 were approximately $3.8 million. The largest component of this was a $2.7 million up-front and additional payments to our manufacturing vendor to secure manufacturing slots necessary for the filing of an IND and dosing of patients in our initial clinical trials. In addition, $834,000 of other external expenses and $326,000 was incurred for consulting fees of the program team, not including allocations of senior management time.

ALS Portfolio, including TAR-DNA binding protein 43 (TDP-43)

The top priority for our scientific validation efforts, largely centered in Dr. Neil Cashman’s laboratory at the University of British Columbia (UBC), is the Company’s ALS portfolio. This portfolio includes antibodies targeting misfolded forms of TDP-43, RACK1, and superoxide dismustase 1 (SOD1). TDP-43 is the focus of the PMN267 program. We are conducting both in vitro assays (assessing the impact of the drug on patient-derived motor neuron cell lines) and in vivo assays (mouse model) and expect initial data in the first half of 2022. In addition, we are exploring different therapeutic modalities in our ALS portfolio. We have disclosed data from our proof of concept work exploring “intrabody” versions of TDP-43 antibodies, a research proxy for a vectorized antibody in a gene therapy vector. We believe this therapeutic approach could enhance therapeutic benefit inside the motor neurons where misfolded TDP-43 aggregates are a root cause of disease pathology, leading to toxic misfolding of other proteins including RACK1 and SOD1. ProMIS’ capability to create highly selective antibodies is most critical in this application, since physiologically important TDP-43 is active inside the neuron and should be avoided by the intrabodies in order to reduce the possibility of harmful side effects. Based on the characterization of selected antibodies/intrabodies to date, we have declared PMN267 as our lead product candidate for the treatment of ALS. In addition, with world expert RNA scientist Dr. Michelle Hastings, ProMIS is exploring antisense oligonucleotide (ASO) therapeutic approaches, and with Dr. Justin Yerbury, is exploring protein degradation (PROTACS) approaches in ALS.

While targeting individual misfolded proteins is expected to provide a benefit, we believe an optimal disease modifying therapeutic approach to ALS may require addressing multiple misfolded protein targets (TDP-43, RACK1, and SOD1), with different modalities (antibody, gene therapy vectorized antibody, ASO, PROTAC). We are exploring the scientific interaction between therapies addressing these various targets, and our goal is to identify and develop a portfolio of complementary therapies that alone and/or together may play a significant role in effectively treating disease.

In the six months ended December 31, 2021, our total expenditures for the ALS portfolio were $299,000, not including allocations of senior management time.

Other key projects

In the six months ended December 31, 2021 we made significant progress on other key projects, in addition to our top priorities PMN310 for AD and PMN267 for ALS. We have engaged with a leading global expert in alpha synuclein to collaborate on further in vitro and in vivo validation of our potential therapies targeting alpha synuclein, both as extracellular antibodies and as intrabodies. Based on the characterization of selected antibodies to date, we have declared PMN442 as our lead alpha synuclein product candidate. Data from in vivo testing in mouse disease models are expected in the second half of 2022.

In our amyloid vaccine program, based on successful pilot work, University of Saskatchewan vaccine and infectious disease organization (VIDO) is conducting mouse studies in collaboration with ProMIS for the development of an optimized vaccine against Alzheimer’s disease, conjugating our peptide antigens to a carrier protein in formulation with an adjuvant. David Wishart, our Chief Physics Officer, and his team, are pursuing multiple novel targets including DISC1 involved in the pathogenesis of schizophrenia.

Recent Corporate Highlights

On May 12, 2021, Rudolph Tanzi, Ph.D., was appointed as the Chair of the Company’s Scientific Advisory Board (SAB). Dr. Tanzi is the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard University and Vice-Chair of Neurology, Director of the Genetics and Aging Research Unit, and Co-Director of the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital.

On May 21, 2021, the Company re-initiated the path to an IND application for PMN310 in Alzheimer’s with the start of producer cell line development. This key first step in the manufacturing of antibody therapeutics is being conducted by Selexis, SA, using its proprietary SUREtechnology Platform™.

On May 27, 2021, Dr. David Wishart, Distinguished University Professor in the Departments of Biological Sciences and Computing Science at the University of Alberta, was appointed as Chief Physics Officer.

On June 3, 2021, the Company announced that it had filed a preliminary Prospectus with the securities regulators in each of the provinces and territories of Canada, except Quebec. The Prospectus, when made final, will allow the Company to make offerings of common shares, warrants, units, debt securities, subscription receipts, convertible securities or any combination thereof for up to an aggregate total of US$50 million during the 25-month period that the Prospectus is effective.

On July 2, 2021, the Company announced the voting results of its annual meeting of shareholders held on June 30, 2021, in Vancouver, British Columbia, Canada. All resolutions described in the Management Proxy Circular and placed before the meeting were approved by the shareholders.

On July 8, 2021, the Company announced that it had filed and obtained a receipt for the Prospectus with the securities regulators in each of the provinces and territories of Canada, except Quebec.

On August 25, 2021, the Company announced the closing of a public offering for gross proceeds of US$20,125,000 (CDN$25,522,525).

On October 7, 2021, ProMIS announced that it would hold a special general meeting of shareholders (the “Special Meeting”) on December 1, 2021. The Company set October 18, 2021, as the record date for the Special Meeting. The purpose of the Special Meeting was to ask shareholders to grant the Board the authority, exercisable in the Board’s discretion, to consolidate (or reverse split) the Company’s issued and outstanding common shares in furtherance of a potential listing of the Company’s shares on a stock exchange in the United States, subject to meeting applicable quantitative and qualitative listing standards of such stock exchange. There can be no assurance that the Company will complete a listing on a stock exchange in the United States.

On December 2, 2021, the shareholders of the Company passed the share consolidation resolution at its special general meeting of shareholders.

On January 18, 2022, ProMIS appointed Dr. Carsten Korth to its SAB.

On January 27, 2022, ProMIS appointed Dr. Cheryl Wellington to its SAB.

On February 3, 2022, ProMIS appointed Dr. Guy Rouleau and Dr. Alain Dagher to its Scientific Advisory Board.

Financial highlights as of and for the year ended December 31, 2021, include:

• In March 2021, the Company completed a US$7.0 million (CDN$8.7 million) private placement of unsecured convertible debentures (Debentures).
  
  
• In August 2021, the Company raised gross proceeds of $25,522,525 ($23,426,746 net of share issuance costs).
  
  
• On December 31, 2021, the Company had funds available for operating activities (cash, cash equivalents and short-term investments) of $21,486,042, as compared to $1,071,004 at December 31, 2020. Our cash is sufficient to finance the Company’s operations through the end of 2023.
  
  

Additions to Board of Directors

• On May 19, 2021, the Company appointed Neil Warma, to the Company’s Board of Directors. Mr. Warma has been a healthcare entrepreneur for more than 25 years having managed and advised numerous biotechnology and pharmaceutical companies.
• On September 1, 2021, the Company appointed Josh Mandel-Brehm to the Board of Directors. Mr. Mandel-Brehm has held various key business development and operations leadership roles at leading biotechnology companies.
• On September 23, 2021, the Company appointed Maggie Shafmaster, JD, Ph.D., to the Board of Directors. Dr. Shafmaster has approximately 30 years of experience providing intellectual property advice to biotechnology and pharmaceutical industries.
  
  

Senior Management Team

On October 22, 2021, the Company announced the expansion of its senior management team. The following changes were announced:

• Eugene Williams, formerly Executive Chairman, takes on the role of Chairman and Chief Executive Officer (“CEO”), with immediate effect.
• Dr. Elliot Goldstein resigned from his current role as CEO with immediate effect and continues to support us as President and special consultant to the CEO.
• Gavin Malenfant joined our senior management team as Chief Operating Officer. Mr. Malenfant brings more than 30 years of biopharmaceutical experience to our team, with special focus on providing expert management and oversight of drug development programs. The top priority in the near term will be to support the timely development of the PMN310 program to completion of IND enabling activities, anticipated in the second half of 2022. 
  
  

Financial Results

Results of Operations – For the years ended December 31, 2021 and 2020

The following table summarizes our results of operations for the years ended December 31, 2021 and 2020:

		Years Ended
		December 31,
		2021				2020				Change
Revenues		$	16,410			$	1,787			$	14,623
Operating expenses
Research and development			6,310,299				3,183,149				3,127,150
General and administrative			4,224,609				2,481,030				1,743,579
Total operating expenses			10,534,908				5,664,179				4,870,729
Loss from operations			10,518,498				5,662,392				4,856,106
Other expense			1,265,917				–				1,265,917
Net loss		$	11,784,415			$	5,662,392			$	6,122,023

Revenues

The increase in revenues in the year ended December 31, 2021 represent royalties received on the Company’s assays.

Research and Development

Research and development expenses consist of the following:

		Years Ended
		December 31,
		2021				2020				Change
Direct research and development expenses by program:		$	4,293,649			$	976,700			$	3,316,949
Indirect research and development expenses:
Personnel related (including stock-based compensation)			812,278				1,672,145				(859,867	)
Consulting expense			588,164				173,712				414,452
Patent expense			557,957				344,864				213,093
Other operating costs			58,251				15,728				42,523
Total research and development expenses		$	6,310,299			$	3,183,149			$	3,127,150

The increase in research and development expense for the year ended December 31, 2021, compared to the year ended December 31, 2020, reflects increased costs associated with external contract research organizations for internal programs of $3,316,949 as the Company ramps up key internal programs and contract research organization costs, increased patent expense of $213,093 due to increased maintenance and filing fees, increased consulting expense of $414,452 and increase in amortization of property and equipment and intangible asset of $42,523 offset by decreased contract salaries and associated costs of $859,867 due to reduction in compensation to management and attrition of contracted staff and decreased share-based compensation of $154,015 due to forfeiture of unvested/vested share options due to termination of consulting arrangement.

General and Administrative

General and administrative expenses consist of the following:

		Years Ended December 31,
		2021				2020				Change
		(in thousands)
Personnel related (including stock-based compensation)		$	1,279,197			$	1,191,967			$	87,230
Professional and consulting fees			2,801,237				1,311,427				1,489,810
Facility-related and other			144,175				(22,364	)			166,539
Total general and administrative expenses		$	4,224,609			$	2,481,030			$	1,743,579

The increase for the year ended December 31, 2021, compared to the same period in 2020, is primarily attributable to an increase in legal expenses of $159,113, increased other professional, legal and consulting fees of 423,378, additional one-time fees of $459,051 related to a potential listing on a stock exchange in the United States, (subject to meeting applicable quantitative and qualitative listing standards of such stock exchange), increased share-based compensation of $306,695 related to the grant of share options, expensing of share issuance costs associated with the issuance of warrants in the August 2021 financing and base shelf costs of $717,806 and foreign exchange of expense of $166,539 on U.S. denominated assets and liabilities offset by a reduction in contracted corporate salaries and associated facility costs of $219,465 due to reduction in compensation to management and attrition of contracted staff and a decreased investor relations of $332,558 due to a reduction of investor relation activities and consultants.   Note that there can be no assurance that the Company will complete a listing on a stock exchange in the United States.  

Other Expense

The increase in other expense is primarily the valuation of the derivative liability associated with the convertible debenture financing and associated interest expense of $2,990,375 offset by the decrease in fair value of the warrant liability of $1,411,467 and the gain on the sale of lab equipment of $75,198.

About ProMIS Neurosciences, Inc.

ProMIS Neurosciences, Inc. is a development stage biotechnology company focused on discovering and developing antibody therapeutics selectively targeting toxic oligomers implicated in the development and progression of neurodegenerative diseases, in particular Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). The Company’s proprietary target discovery engine is based on the use of two complementary techniques. The Company applies its thermodynamic, computational discovery platform -ProMIS™ and Collective Coordinates – to predict novel targets known as Disease Specific Epitopes on the molecular surface of misfolded proteins. Using this unique approach, the Company is developing novel antibody therapeutics for AD, ALS and PD. ProMIS is headquartered in Toronto, Ontario, with offices in Cambridge, Massachusetts. ProMIS is listed on the Toronto Stock Exchange under the symbol PMN, and on the OTCQB Venture Market under the symbol ARFXF.

Visit us at www.promisneurosciences.com, follow us on Twitter and LinkedIn

For Investor Relations please contact:
Alpine Equity Advisors
Nicholas Rigopulos, President
nick@alpineequityadv.com
Tel. 617 901-0785

The TSX has not reviewed and does not accept responsibility for the adequacy or accuracy of this release. Certain information in this news release constitutes forward-looking statements and forward-looking information (collectively, ??”forward-looking information”) within the meaning of applicable securities laws. In some cases, but not necessarily in all cases, forward–looking information can be identified by the ?use of forward-looking terminology such as “plans”, “targets”, “expects” or “does not expect”, “is expected”, “an opportunity exists”, ??”is positioned”, “estimates”, “intends”, “assumes”, “anticipates” or “does not anticipate” or “believes”, or variations of such words and ?phrases or state that certain actions, events or results “may”, “could”, “would”, “might”, “will” or “will be taken”, “occur” or “be ?achieved”. In addition, any statements that refer to expectations, projections or other characterizations of future events or ?circumstances contain forward-looking information. ?Specifically, this news release contains forward-looking information relating to future management and Board composition of the Company; the potential listing of the Company’s shares on a stock exchange in the United States; the expectation that markets will rebound; the expected completion date of various studies and timelines for the development of assays; the potential benefits of targeting misfolded proteins; and the timing of PMN 442 in vivo testing data in mouse disease models. Statements containing forward-looking information are not historical facts but instead represent management’s current ?expectations, estimates and projections regarding the future of our business, future plans, strategies, projections, anticipated events ?and trends, the economy and other future conditions. Forward-looking information is necessarily based on a number of opinions, ?assumptions and estimates that, while considered reasonable by the Company as of the date of this news release, are subject to ?known and unknown risks, uncertainties, assumptions and other factors that may cause the actual results, level of activity, ?performance or achievements to be materially different from those expressed or implied by such forward-looking information. Important factors that could cause actual results and financial condition to differ materially from those indicated in the forward-looking information include, among others, the factors discussed throughout the “Risk Factors” section of the Company’s most recently filed annual information form available on www.SEDAR.com. Except as required by applicable securities laws, the Company undertakes no obligation to publicly update any forward-looking information, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

Source: ProMIS Neurosciences Inc.

ProMIS Neurosciences Announces Fiscal Year 2021 Results

News and Market Data on ProMIS Neurosciences

 

TORONTO, Ontario and CAMBRIDGE, Massachusetts , March 17, 2022 (GLOBE NEWSWIRE) — ProMIS Neurosciences, Inc. (TSX: PMN) (OTCQB: ARFXF) (“ProMIS” or the “Company”), a biotechnology company focused on the discovery and development of antibody therapeutics targeting misfolded proteins such as toxic oligomers, implicated in the development of neurodegenerative diseases, today announced its operational and financial results for the fiscal year ended December 31, 2021.

“2021 was an excellent year for ProMIS including strong capital formation which enabled us to advance and expand our portfolio of differentiated therapeutic product candidates such as Alzheimer’s disease (AD), ALS, and Schizophrenia,” said Gene Williams, ProMIS’ Chairman and CEO.   “We feel privileged that leading global experts continue to join our Scientific Advisory Board (SAB), accomplished executives are joining our Board of Directors, and that we have been able to supplement our strong management team, and we expect to continue those trends. We were grateful for the strong shareholder support for the resolution necessary to qualify for a potential listing on a major North American stock exchange presuming we meet the required listing standards. While biotechnology markets and specific disease sectors within biotechnology have cyclical ups and downs, we are well positioned to continue making substantive progress in our programs that could allow us to capitalize when markets rebound, as we believe they will.”

PMN310, an antibody selective for toxic oligomers in AD, is ProMIS’ lead product candidate. In the fourth quarter of 2021, the Company made significant progress on the program elements.

Producer cell line development is advancing. The genetic sequence of PMN310 has been transfected into Chinese hamster ovary (CHO) cells, the standard production cells for antibody manufacturing. We have contractually secured manufacturing slots for material to be used in Good Laboratory Practice (GLP) toxicology studies and for current Good Manufacturing Practice (cGMP) material for use in the initial clinical trials of PMN310, if allowed to proceed. In addition, we have contractually secured slots for GLP toxicology studies of various durations in nonhuman primates to support our single ascending dose/multiple ascending dose (SAD/MAD) trials. We have initiated pilot toxicology and pharmacokinetics (PK) studies to provide important information to support our GLP toxicology studies. We expect those PK studies to be completed in the second quarter of 2022. We also have secured slots for pilot and GLP tissue cross reactivity (TCR) studies, which are required for an investigational new drug (IND) application, in addition to GLP toxicology. The pilot TCR study was initiated fourth quarter of 2021 with an expected completion in second quarter 2022. Development of assays to measure drug levels in both nonhuman primate and human studies have been initiated and are expected to complete development in second quarter of 2022. Vendors have been contracted to perform these assays for our GLP studies.

In addition, in March 2022, we announced the results from a study assessing chronic systemic administration of PMN310 in a transgenic mouse model of Alzheimer’s disease, where the cognitive deficit is driven by toxic amyloid-beta oligomers. The results were positive, showing that PMN310 prevented a cognitive deficit as measured by performance in the water maze task.   

Cash expenditures for PMN310 in the six months ended December 31, 2021 were approximately $3.8 million. The largest component of this was a $2.7 million up-front and additional payments to our manufacturing vendor to secure manufacturing slots necessary for the filing of an IND and dosing of patients in our initial clinical trials. In addition, $834,000 of other external expenses and $326,000 was incurred for consulting fees of the program team, not including allocations of senior management time.

ALS Portfolio, including TAR-DNA binding protein 43 (TDP-43)

The top priority for our scientific validation efforts, largely centered in Dr. Neil Cashman’s laboratory at the University of British Columbia (UBC), is the Company’s ALS portfolio. This portfolio includes antibodies targeting misfolded forms of TDP-43, RACK1, and superoxide dismustase 1 (SOD1). TDP-43 is the focus of the PMN267 program. We are conducting both in vitro assays (assessing the impact of the drug on patient-derived motor neuron cell lines) and in vivo assays (mouse model) and expect initial data in the first half of 2022. In addition, we are exploring different therapeutic modalities in our ALS portfolio. We have disclosed data from our proof of concept work exploring “intrabody” versions of TDP-43 antibodies, a research proxy for a vectorized antibody in a gene therapy vector. We believe this therapeutic approach could enhance therapeutic benefit inside the motor neurons where misfolded TDP-43 aggregates are a root cause of disease pathology, leading to toxic misfolding of other proteins including RACK1 and SOD1. ProMIS’ capability to create highly selective antibodies is most critical in this application, since physiologically important TDP-43 is active inside the neuron and should be avoided by the intrabodies in order to reduce the possibility of harmful side effects. Based on the characterization of selected antibodies/intrabodies to date, we have declared PMN267 as our lead product candidate for the treatment of ALS. In addition, with world expert RNA scientist Dr. Michelle Hastings, ProMIS is exploring antisense oligonucleotide (ASO) therapeutic approaches, and with Dr. Justin Yerbury, is exploring protein degradation (PROTACS) approaches in ALS.

While targeting individual misfolded proteins is expected to provide a benefit, we believe an optimal disease modifying therapeutic approach to ALS may require addressing multiple misfolded protein targets (TDP-43, RACK1, and SOD1), with different modalities (antibody, gene therapy vectorized antibody, ASO, PROTAC). We are exploring the scientific interaction between therapies addressing these various targets, and our goal is to identify and develop a portfolio of complementary therapies that alone and/or together may play a significant role in effectively treating disease.

In the six months ended December 31, 2021, our total expenditures for the ALS portfolio were $299,000, not including allocations of senior management time.

Other key projects

In the six months ended December 31, 2021 we made significant progress on other key projects, in addition to our top priorities PMN310 for AD and PMN267 for ALS. We have engaged with a leading global expert in alpha synuclein to collaborate on further in vitro and in vivo validation of our potential therapies targeting alpha synuclein, both as extracellular antibodies and as intrabodies. Based on the characterization of selected antibodies to date, we have declared PMN442 as our lead alpha synuclein product candidate. Data from in vivo testing in mouse disease models are expected in the second half of 2022.

In our amyloid vaccine program, based on successful pilot work, University of Saskatchewan vaccine and infectious disease organization (VIDO) is conducting mouse studies in collaboration with ProMIS for the development of an optimized vaccine against Alzheimer’s disease, conjugating our peptide antigens to a carrier protein in formulation with an adjuvant. David Wishart, our Chief Physics Officer, and his team, are pursuing multiple novel targets including DISC1 involved in the pathogenesis of schizophrenia.

Recent Corporate Highlights

On May 12, 2021, Rudolph Tanzi, Ph.D., was appointed as the Chair of the Company’s Scientific Advisory Board (SAB). Dr. Tanzi is the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard University and Vice-Chair of Neurology, Director of the Genetics and Aging Research Unit, and Co-Director of the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital.

On May 21, 2021, the Company re-initiated the path to an IND application for PMN310 in Alzheimer’s with the start of producer cell line development. This key first step in the manufacturing of antibody therapeutics is being conducted by Selexis, SA, using its proprietary SUREtechnology Platform™.

On May 27, 2021, Dr. David Wishart, Distinguished University Professor in the Departments of Biological Sciences and Computing Science at the University of Alberta, was appointed as Chief Physics Officer.

On June 3, 2021, the Company announced that it had filed a preliminary Prospectus with the securities regulators in each of the provinces and territories of Canada, except Quebec. The Prospectus, when made final, will allow the Company to make offerings of common shares, warrants, units, debt securities, subscription receipts, convertible securities or any combination thereof for up to an aggregate total of US$50 million during the 25-month period that the Prospectus is effective.

On July 2, 2021, the Company announced the voting results of its annual meeting of shareholders held on June 30, 2021, in Vancouver, British Columbia, Canada. All resolutions described in the Management Proxy Circular and placed before the meeting were approved by the shareholders.

On July 8, 2021, the Company announced that it had filed and obtained a receipt for the Prospectus with the securities regulators in each of the provinces and territories of Canada, except Quebec.

On August 25, 2021, the Company announced the closing of a public offering for gross proceeds of US$20,125,000 (CDN$25,522,525).

On October 7, 2021, ProMIS announced that it would hold a special general meeting of shareholders (the “Special Meeting”) on December 1, 2021. The Company set October 18, 2021, as the record date for the Special Meeting. The purpose of the Special Meeting was to ask shareholders to grant the Board the authority, exercisable in the Board’s discretion, to consolidate (or reverse split) the Company’s issued and outstanding common shares in furtherance of a potential listing of the Company’s shares on a stock exchange in the United States, subject to meeting applicable quantitative and qualitative listing standards of such stock exchange. There can be no assurance that the Company will complete a listing on a stock exchange in the United States.

On December 2, 2021, the shareholders of the Company passed the share consolidation resolution at its special general meeting of shareholders.

On January 18, 2022, ProMIS appointed Dr. Carsten Korth to its SAB.

On January 27, 2022, ProMIS appointed Dr. Cheryl Wellington to its SAB.

On February 3, 2022, ProMIS appointed Dr. Guy Rouleau and Dr. Alain Dagher to its Scientific Advisory Board.

Financial highlights as of and for the year ended December 31, 2021, include:

• In March 2021, the Company completed a US$7.0 million (CDN$8.7 million) private placement of unsecured convertible debentures (Debentures).
  
  
• In August 2021, the Company raised gross proceeds of $25,522,525 ($23,426,746 net of share issuance costs).
  
  
• On December 31, 2021, the Company had funds available for operating activities (cash, cash equivalents and short-term investments) of $21,486,042, as compared to $1,071,004 at December 31, 2020. Our cash is sufficient to finance the Company’s operations through the end of 2023.
  
  

Additions to Board of Directors

• On May 19, 2021, the Company appointed Neil Warma, to the Company’s Board of Directors. Mr. Warma has been a healthcare entrepreneur for more than 25 years having managed and advised numerous biotechnology and pharmaceutical companies.
• On September 1, 2021, the Company appointed Josh Mandel-Brehm to the Board of Directors. Mr. Mandel-Brehm has held various key business development and operations leadership roles at leading biotechnology companies.
• On September 23, 2021, the Company appointed Maggie Shafmaster, JD, Ph.D., to the Board of Directors. Dr. Shafmaster has approximately 30 years of experience providing intellectual property advice to biotechnology and pharmaceutical industries.
  
  

Senior Management Team

On October 22, 2021, the Company announced the expansion of its senior management team. The following changes were announced:

• Eugene Williams, formerly Executive Chairman, takes on the role of Chairman and Chief Executive Officer (“CEO”), with immediate effect.
• Dr. Elliot Goldstein resigned from his current role as CEO with immediate effect and continues to support us as President and special consultant to the CEO.
• Gavin Malenfant joined our senior management team as Chief Operating Officer. Mr. Malenfant brings more than 30 years of biopharmaceutical experience to our team, with special focus on providing expert management and oversight of drug development programs. The top priority in the near term will be to support the timely development of the PMN310 program to completion of IND enabling activities, anticipated in the second half of 2022. 
  
  

Financial Results

Results of Operations – For the years ended December 31, 2021 and 2020

The following table summarizes our results of operations for the years ended December 31, 2021 and 2020:

		Years Ended
		December 31,
		2021				2020				Change
Revenues		$	16,410			$	1,787			$	14,623
Operating expenses
Research and development			6,310,299				3,183,149				3,127,150
General and administrative			4,224,609				2,481,030				1,743,579
Total operating expenses			10,534,908				5,664,179				4,870,729
Loss from operations			10,518,498				5,662,392				4,856,106
Other expense			1,265,917				–				1,265,917
Net loss		$	11,784,415			$	5,662,392			$	6,122,023

Revenues

The increase in revenues in the year ended December 31, 2021 represent royalties received on the Company’s assays.

Research and Development

Research and development expenses consist of the following:

		Years Ended
		December 31,
		2021				2020				Change
Direct research and development expenses by program:		$	4,293,649			$	976,700			$	3,316,949
Indirect research and development expenses:
Personnel related (including stock-based compensation)			812,278				1,672,145				(859,867	)
Consulting expense			588,164				173,712				414,452
Patent expense			557,957				344,864				213,093
Other operating costs			58,251				15,728				42,523
Total research and development expenses		$	6,310,299			$	3,183,149			$	3,127,150

The increase in research and development expense for the year ended December 31, 2021, compared to the year ended December 31, 2020, reflects increased costs associated with external contract research organizations for internal programs of $3,316,949 as the Company ramps up key internal programs and contract research organization costs, increased patent expense of $213,093 due to increased maintenance and filing fees, increased consulting expense of $414,452 and increase in amortization of property and equipment and intangible asset of $42,523 offset by decreased contract salaries and associated costs of $859,867 due to reduction in compensation to management and attrition of contracted staff and decreased share-based compensation of $154,015 due to forfeiture of unvested/vested share options due to termination of consulting arrangement.

General and Administrative

General and administrative expenses consist of the following:

		Years Ended December 31,
		2021				2020				Change
		(in thousands)
Personnel related (including stock-based compensation)		$	1,279,197			$	1,191,967			$	87,230
Professional and consulting fees			2,801,237				1,311,427				1,489,810
Facility-related and other			144,175				(22,364	)			166,539
Total general and administrative expenses		$	4,224,609			$	2,481,030			$	1,743,579

The increase for the year ended December 31, 2021, compared to the same period in 2020, is primarily attributable to an increase in legal expenses of $159,113, increased other professional, legal and consulting fees of 423,378, additional one-time fees of $459,051 related to a potential listing on a stock exchange in the United States, (subject to meeting applicable quantitative and qualitative listing standards of such stock exchange), increased share-based compensation of $306,695 related to the grant of share options, expensing of share issuance costs associated with the issuance of warrants in the August 2021 financing and base shelf costs of $717,806 and foreign exchange of expense of $166,539 on U.S. denominated assets and liabilities offset by a reduction in contracted corporate salaries and associated facility costs of $219,465 due to reduction in compensation to management and attrition of contracted staff and a decreased investor relations of $332,558 due to a reduction of investor relation activities and consultants.   Note that there can be no assurance that the Company will complete a listing on a stock exchange in the United States.  

Other Expense

The increase in other expense is primarily the valuation of the derivative liability associated with the convertible debenture financing and associated interest expense of $2,990,375 offset by the decrease in fair value of the warrant liability of $1,411,467 and the gain on the sale of lab equipment of $75,198.

About ProMIS Neurosciences, Inc.

ProMIS Neurosciences, Inc. is a development stage biotechnology company focused on discovering and developing antibody therapeutics selectively targeting toxic oligomers implicated in the development and progression of neurodegenerative diseases, in particular Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). The Company’s proprietary target discovery engine is based on the use of two complementary techniques. The Company applies its thermodynamic, computational discovery platform -ProMIS™ and Collective Coordinates – to predict novel targets known as Disease Specific Epitopes on the molecular surface of misfolded proteins. Using this unique approach, the Company is developing novel antibody therapeutics for AD, ALS and PD. ProMIS is headquartered in Toronto, Ontario, with offices in Cambridge, Massachusetts. ProMIS is listed on the Toronto Stock Exchange under the symbol PMN, and on the OTCQB Venture Market under the symbol ARFXF.

Visit us at www.promisneurosciences.com, follow us on Twitter and LinkedIn

For Investor Relations please contact:
Alpine Equity Advisors
Nicholas Rigopulos, President
nick@alpineequityadv.com
Tel. 617 901-0785

The TSX has not reviewed and does not accept responsibility for the adequacy or accuracy of this release. Certain information in this news release constitutes forward-looking statements and forward-looking information (collectively, ??”forward-looking information”) within the meaning of applicable securities laws. In some cases, but not necessarily in all cases, forward–looking information can be identified by the ?use of forward-looking terminology such as “plans”, “targets”, “expects” or “does not expect”, “is expected”, “an opportunity exists”, ??”is positioned”, “estimates”, “intends”, “assumes”, “anticipates” or “does not anticipate” or “believes”, or variations of such words and ?phrases or state that certain actions, events or results “may”, “could”, “would”, “might”, “will” or “will be taken”, “occur” or “be ?achieved”. In addition, any statements that refer to expectations, projections or other characterizations of future events or ?circumstances contain forward-looking information. ?Specifically, this news release contains forward-looking information relating to future management and Board composition of the Company; the potential listing of the Company’s shares on a stock exchange in the United States; the expectation that markets will rebound; the expected completion date of various studies and timelines for the development of assays; the potential benefits of targeting misfolded proteins; and the timing of PMN 442 in vivo testing data in mouse disease models. Statements containing forward-looking information are not historical facts but instead represent management’s current ?expectations, estimates and projections regarding the future of our business, future plans, strategies, projections, anticipated events ?and trends, the economy and other future conditions. Forward-looking information is necessarily based on a number of opinions, ?assumptions and estimates that, while considered reasonable by the Company as of the date of this news release, are subject to ?known and unknown risks, uncertainties, assumptions and other factors that may cause the actual results, level of activity, ?performance or achievements to be materially different from those expressed or implied by such forward-looking information. Important factors that could cause actual results and financial condition to differ materially from those indicated in the forward-looking information include, among others, the factors discussed throughout the “Risk Factors” section of the Company’s most recently filed annual information form available on www.SEDAR.com. Except as required by applicable securities laws, the Company undertakes no obligation to publicly update any forward-looking information, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

Source: ProMIS Neurosciences Inc.

Thursday, March 17, 2022

Baudax Bio (BXRX)
Fourth Quarter 2021 Reported; Major Expense Reductions Announced

Baudax Bio is a biopharmaceutical company focused on developing therapies for post-operative pain, peri-operative pain, and anesthesia. The company currently has one approved therapy in ANJESO for post-operative pain. Proprietary ANJESO (meloxicam) injection is the first and only once-daily IV analgesic. The company also has a pipeline of early-stage candidates with two novel neuromuscular blocking agents (NMBAs), a proprietary related reversal agent to their NMBAs, and Dex-IN, an intranasal formulation of dexmedetomidine (Dex) that has sedative, analgesic, and anti-anxiety properties.

Gregory Aurand, Senior Research Analyst, Healthcare Services & Medical Devices, Noble Capital Markets, Inc.

Refer to the full report for the price target, fundamental analysis, and rating.

4Q 2021 revenues reported. Yesterday, Baudax Bio released 4Q and FY 2021 results. Despite better-than-expected formulary wins, Covid related elective procedures remained muted in regions of the U.S. While solid, 4Q revenues of $.4 million, up 426%, missed our $0.55 million estimate. FY 2021 reported revenues of $1.08 million, up 119%, missed our $1.23 million estimate.

Company is reducing headcount and expenses.  The company is implementing a workplace reduction plan to curtail expenses and reduce need for capital. The plan is expected to reduce headcount 80%. The company expects approximately $4.0 million in severance and related costs to be taken by end of 2Q 2022. Cash burn will be substantially reduced in 2H 2022 and beyond …

This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).

*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.