Pharmaceutical giant Bristol Myers Squibb made a bold move into neuroscience today, announcing the $14 billion acquisition of clinical-stage biotech Karuna Therapeutics. The massive deal provides Bristol Myers with Karuna’s lead drug candidate, KarXT, a potential new treatment for schizophrenia and other psychiatric disorders.
KarXT could be the first drug in its class approved for schizophrenia in decades. The market for schizophrenia drugs is estimated at over $7 billion globally. If approved, KarXT is projected to achieve multi-billion dollar peak sales. Bristol Myers is betting the experimental medicine could transform treatment for millions struggling with serious mental illness.
This acquisition is the latest in a wave of big pharma interest in the emerging neuroscience space. Companies are eager to find new approaches to historically hard-to-treat psychiatric conditions like schizophrenia, depression and Alzheimer’s disease.
Smaller biotechs like Karuna have led the charge, developing novel therapies targeting neurological mechanisms of psychiatric disorders. But larger players like Bristol Myers have taken notice of the promise of these new technologies.
Karuna’s KarXT combines xanomeline, a novel muscarinic receptor agonist, with trospium chloride, an FDA-approved muscarinic receptor antagonist. Early clinical results show this approach reduces side effects and improves efficacy compared to current schizophrenia drugs.
In late-stage clinical trials, KarXT demonstrated statistically significant and clinically meaningful improvements in schizophrenia symptoms. Patients experienced rapid reductions in hallucinations and delusions with far fewer problematic side effects like sedation.
Based on positive Phase 3 data, Karuna submitted a New Drug Application for KarXT in schizophrenia in mid-2022. The FDA accepted the application and set a PDUFA goal date of September 2023 for a potential approval.
Clearly Bristol Myers feels confident about KarXT’s chances, agreeing to pay $28.5 billion upfront in cash to finalize the acquisition. Karuna shareholders will also be eligible for up to $3.5 billion in milestone payments if KarXT reaches certain commercial goals.
For Bristol Myers, the move signals a push into neuroscience and psychiatric disease, an area it has not traditionally emphasized. But the company likely sees major growth potential, given the prevalence of mental illness and the need for better treatments.
Almost 3% of the U.S. population suffers from schizophrenia. Another 17% experience some other mental illness like depression, bipolar disorder or PTSD. Existing drugs fail to adequately manage symptoms for many patients and carry tolerability issues that lead to poor compliance.
Doctors and patients are eagerly awaiting novel therapies like KarXT that balance safety and efficacy. Karuna is also exploring KarXT’s potential in dementia-related psychosis and other indications beyond schizophrenia.
The lucrative deal builds on other recent big-ticket acquisitions for Bristol Myers as the company looks to expand its portfolio. Earlier this year, Bristol Myers acquired cancer biotech Turning Point Therapeutics for $3.2 billion and the oncology company MyoKardia for $13 billion.
But the Karuna purchase represents Bristol Myers’ biggest bet yet on the emerging neuroscience space. It’s the second largest biopharma acquisition announced in 2022 after Pfizer’s $43 billion buyout of cancer drugmaker Seagen.
Other large pharmaceutical companies have also signed deals to access neuropsychiatric drug candidates. AbbVie recently acquired an option to purchase Alector’s experimental Alzheimer’s therapy for up to $2.2 billion. And Eli Lilly collaborated with NextCure on novel immuno-oncology approaches for treating mental illness.
As more novel mechanisms like KarXT arrive, expect growing competition among pharma giants to capture market share. Bristol Myers struck first with today’s monumental acquisition, but likely won’t be the last looking to neuroscience for future growth.
Cambridge-based gene therapy developer Bluebird Bio announced a public offering of $150 million in common stock to raise capital supporting its three approved treatments and provide working capital.
The pioneer in gene therapies will offer shares on the NASDAQ under the ticker symbol BLUE, with underwriters granted a 30-day option to purchase an additional $22.5 million in stock. Bluebird stated the final size and terms remain subject to market conditions.
Goldman Sachs and J.P. Morgan are serving as joint book runners on the deal, with Raymond James as co-manager on the offering. All shares sold will come directly from Bluebird Bio.
Proceeds from the public stock sale will specifically further commercialization, manufacturing, and launch efforts behind the company’s newly approved gene therapies – Zynteglo for beta thalassemia, Skysona for cerebral adrenoleukodystrophy, and Lyfgenia for sickle cell disease.
The capital raise also provides balance sheet support as Bluebird continues its transition into a fully-integrated commercial biotech selling proprietary therapies targeting rare diseases.
Analysts see the offering as a move to seize current investor enthusiasm and strengthen Bluebird’s financial position after a turbulent few years adjusting to regulatory setbacks.
With three potent gene therapies now approved since August 2022, Bluebird looks to ride accelerating momentum as its treatments reach more patients globally. But the specialized nature of gene therapy production and administration constrains rapid scaling despite massive market opportunities.
Hefty expenses can also accrue during the early stages of drug launches pending insurance coverage and reimbursement decisions country by country.
Tuesday’s proposed $150 million offering suggests management sees room to accelerate growth in 2024 while demand runs hot for novel gene therapies.
Gene Therapies Target Root Causes of Diseases by Manipulating Genes
The permanent gene corrections from one-time gene therapy represent potential cures promising to revolutionize treatment for blood disorders, cancers, inherited disorders and degenerative diseases.
After gene therapy showed immense promise in the 2010s, developmental and safety hurdles caused temporary setbacks for the emerging category.
But breakthrough approvals over the past 18 months from Bluebird and others have reinvigorated investor appetite to fund the next generation of radical genetic medicines now reaching patients in need.
While small in patient size, the market chances to generate multi-billion sales treating high unmet needs in rare diseases with no other solutions for the underlying condition.
Goldman Sachs and JPMorgan’s involvement arranging Bluebird’s latest stock sale reflects rising investor intrigue and renewed confidence in realizing gene therapy’s paradigm-changing potential after past stumbles.
Still Long Road Ahead as Gene Therapies Slowly Build Adoption
However, analysts caution the road remains long translating hype into real revenues as gene therapy faces entrenched barriers preventing mass adoption anytime soon.
Priced at over $2 million per treatment, gene therapies today dispense more hope than profit for developers. Reimbursement pushback from insurers and intense medical limitations temper growth projections.
Bluebird’s approved drugs currently treat tiny populations measured in the single digit thousands globally. But success establishing coverage helps pave the way for expanding into wider therapeutic indications in time.
With fresh financing now on tap, Bluebird Bio stock offers a investment into a maturing gene therapy leader well-positioned to ride coming decades of medical advancements illuminating genetics’ role beating back disease.
Yet expectations likely stay muted near-term for all gene therapy plays absent key inflection events bringing more treatments past global regulatory gates.
A wave of multibillion dollar buyouts has swept the beaten-down biotech sector in recent months, marking a potential turning point for an industry hammered throughout 2022 – 2023.
With valuations of public companies still depressed, flush private investors have stepped up acquisitions of promising drug developers to bolster pipelines for the long-term. And in a bullish sign for the strategic direction of the space, therapeutics targeting high unmet needs and novel modalities remain key areas of focus amid dealmaking.
Market observers viewed the unsolicited, $58 per share bid as a credible benchmark of intrinsic value vigilantly researched by a strategic acquirer. Immediately in the deal aftermath, similar development-stage oncology names rallied sharply as traders priced in new takeout probabilities.
In fact, suitors moved swiftly to capitalize on improved biotech sentiment, with Horizon Therapeutics agreeing to a $26.4 billion around the same time. The transaction marked 2023’s largest healthcare buyout, further reinforcing peak valuations remain attainable for commercial-stage rare disease names.
Scaling Up to Compete in Gene Therapy
Gene therapy remains one especially alluring area for dealmaking despite lofty price tags. These ultra-rare disease medicines come with cure potential that commands premium sales and reimbursement pricing power.
Recognizing the imperative to bulk up gene therapy capabilities, Pfizer ponied up $5.4 billion to reinforce its genetic medicines pipeline through the acquisition of French outfit Vivet Therapeutics. The move added Vivet’s promising gene therapy for Wilson disease, along with manufacturing strengths across multiple delivery mechanisms.
And gene editing pioneer Sangamo Therapeutics is selling off its cell therapy assets to Sanofi for $700 million as it refocuses efforts around in vivo gene insertion. The deal hands Sanofi disruptive cell therapy technology utilizing precisely engineered zinc fingers to correct disease-causing mutations.
Analysts say more buyouts centered on next-gen platforms are likely on the horizon as drug developers vie for leadership in areas forecast to reshape therapeutic spaces.
Private Capital Eagerly Steps in to Back Innovation
Beyond M&A from strategic acquirers, private equity firms have swooped in to capitalize on depressed biotech valuations. The robust dry powder levels built up during the boom years leave private investors eager to allocate while achieving advantageous cost bases.
Among notable deals, Angel Pond Capital teamed up with life science investor OrbiMed to take gene therapy biotech Generate Biomedicines private for $478 million. The transaction represented a 130% premium to ensure locking up Generate’s base editing technologies believed to be capable of correcting over 75% of known point mutations.
In cybersecurity and enterprise software, sponsor-led take privates had utterly dominated deal flow in 2022. But order books are now once again filling up with biotech buyouts from special purpose acquisition vehicles, highlighting a normalization in deal dynamics after last year’s freeze-out from rate-sensitive private market valuations.
Market Recovery Taking Shape
The fresh upswing in biotech M&A follows a wave of dip buying from some the world’s largest asset managers in shares of industry leaders like Vertex Pharmaceuticals and Regeneron Pharmaceuticals. Warren Buffett’s Berkshire Hathaway has been particularly aggressive stepping in to purchase stakes in key biopharma bluechips.
Meanwhile, the fund-raising backdrop continues improving for earlier stage biotechs as well after deal activity all but shuttered for much of 2023. Multiple debt offerings and venture rounds have successfully priced in recent months, ensuring the all-important continuity of innovation cycling.
With fundamentals stabilizing and access to capital normalizing, the environment for biopharma dealmaking has markedly improved. Expect the momentum to carry through 2024 as drug developers position through M&A for the next, post-pandemic leg higher while private capital readily supports compelling technologies at discounted prices. The long-term health of the biotech ecosystem depends on transactions advancing today’s high-potential assets, and the industry appears to have emerged from its lull ready to strike the necessary deals.
Medical device maker Integra LifeSciences announced today it will purchase Acclarent, a leader in ear, nose and throat (ENT) technologies, from Johnson & Johnson’s Ethicon division for $275 million upfront plus future regulatory milestones. The deal values Acclarent at approximately 2.5 times sales, with the company generating $110 million in revenues during 2022.
For Integra, the acquisition provides an opportunity to significantly expand its footprint beyond neurosurgery and establish the company as a major player in the attractive ENT specialty devices segment. The global ENT market is projected to grow at a 5-6% clip annually, adding an estimated $1 billion in addressable market opportunity for Integra.
Acclarent brings to Integra pioneered balloon dilation platforms for treating chronic sinusitis as well as novel treatments for Eustachian tube dilations. Its flagship products are the only FDA-approved stents for maintaining sinus openings after surgery. Acclarent also provides image guidance systems to assist surgeons with minimally invasive procedures.
The company maintains strong brand awareness and deep clinical relationships after rebuilding its commercial presence following a period of declining sales between 2017-2020.
Integra management sees substantial room for additional share gains in ENT given Acclarent’s leadership in balloon dilation and the generally fragmented supplier landscape in ENT today. The global sinus dilation devices market alone is projected to reach $3.5 billion by 2030, providing a sizable growth pipeline for Acclarent’s portfolio.
Strategic and Financial Benefits
The acquisition furthers Integra’s strategy to complement its legacy strength in neurosurgery with scaled positions across faster-growth clinical applications adjacent to its core.
Integra aims to replicate its #1 share in dural repair for neuro procedures by becoming one of few dominant players in ENT. The company believes the combination of its commercial infrastructure and Acclarent’s innovative portfolio can support above-market growth for the foreseeable future.
Financially, Acclarent is being acquired at an attractive upfront valuation of 2.5 times sales. Integra management expects the deal will be immediately accretive to earnings per share after closing.
Acclarent generated gross margins in line with Integra’s overall company average in 2022, providing opportunities for further margin expansion from operating leverage as the business scales.
The transaction also comes at a time when medtech valuations have declined from their pandemic peaks, enabling Integra to obtain Acclarent at what it believes to be an opportunistic price.
Cultural and Portfolio Fit
Integra CEO Jan De Witte highlighted the cultural alignment between both organizations and focus on restoring patient lives as key rationales behind the deal.
De Witte said, “Acclarent’s culture of pioneering technologies aligns with Integra’s legacy of innovation to transform care and restore patients’ lives. We are looking forward to welcoming the Acclarent employees to the Integra team. Together, we can make a profound impact on the future of ENT and neurosurgery.”
Acclarent will operate as part of Integra’s $1.3 billion Codman Specialty Surgical division focused on neurosurgery. Integra sees substantial opportunities for its neurosurgery and ENT sales teams to collaborate on treating certain brain tumors by leveraging skull base surgical approaches.
Integra also gains access to a robust ENT product development pipeline, including next-generation surgical staplers, powered sinus surgery technologies, and potential new indications for Acclarent’s balloon dilation platforms.
Acclarent’s R&D and regulatory expertise will help accelerate Integra’s internal efforts to bring new generations of minimally invasive surgery products to market.
Smooth Post-Close Integration
Integra expects to retain Acclarent’s entire workforce as part of ensuring a smooth organizational transition after the deal closes. The company aims to operate Acclarent as an independent business unit during the near-term while integrating back-office functions.
Manufacturing operations will continue to be outsourced to third parties and Integra anticipates no supply chain disruptions to Acclarent’s product availability.
The transaction is projected to close by the second quarter of 2024, subject to customary antitrust and regulatory clearances globally. Transition services agreements will provide additional support for up to four years following deal closure.
By maintaining continuity of strategy, personnel and manufacturing, Integra hopes to achieve targeted revenue and cost synergies from the integration of Acclarent, while continuing its above-market growth trajectory in the ENT segment. The addition of Acclarent’s portfolio and innovative roadmap makes this transaction an important step forward in Integra’s strategy to complement leadership in neurosurgery with scaled positions in some of medtech’s most attractive and fastest-growing markets.
Cholesterol Efflux MediatorTM VAR 200 is in development to ameliorate renal lipid accumulation that damages the kidneys’ filtration system, leading to chronic kidney disease and its progression.
WESTON, Fla., Dec. 14, 2023 (GLOBE NEWSWIRE) — ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA; “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of patients with renal and inflammatory diseases who have unmet medical needs, announces selection of contract research organization (“CRO”) George Clinical to manage its Phase 2a clinical trial with Cholesterol Efflux MediatorTM VAR 200 in patients with diabetic kidney disease (DKD). The clinical trial is expected to begin in the first quarter of 2024.
George Clinical is a leading global CRO, headquartered in Sydney, Australia, with more than 500 experienced people in 39 locations providing the full range of clinical trial services to pharmaceutical, medical device, and diagnostic customers for all trial phases, registration, and post-marketing trials. George Clinical, who combines scientific and clinical leadership with expert trial delivery to create distinctive world-class solutions, was the recipient of Citeline’s 2023 Clinical Research Team of the Year. They were recognized for their success in achieving their goals, effective work practices, creative solutions, and meeting major milestones within expected timelines.
“Initiation of the Phase 2a trial in patients with DKD marks a major milestone in the development of Cholesterol Efflux MediatorTM VAR 200 and for ZyVersa. It is the first clinical trial for VAR 200 and will help establish its effectiveness and safety in renal patients, and it will provide valuable insights to guide development for other planned renal indications (focal segmental glomerulosclerosis and Alport syndrome),” said Stephen C. Glover, ZyVersa’s Co-founder, Chief Executive Officer, and Chairman. “We are pleased to partner with George Clinical to manage this important study. With their unparalleled renal research experience in more than 50 chronic renal disease trials and their reputation as a high performing renal CRO, we are confident that our trial will be conducted in an efficient and timely manner to achieve our milestones and advance VAR 200’s development program to the next level.”
“Collaborating with ZyVersa Therapeutics on this trial shows not only our passion for kidney research but also the commitment to provide the necessary clinical research around innovative treatments that could help patients with unmet medical needs,” said George Clinical Chief Medical Officer Maria Ali.
About VAR 200
Cholesterol Efflux MediatorTM VAR 200 (2-hydroxypropyl-beta-cyclodextrin, 2HPβCD) is a phase 2a-ready drug in development to ameliorate renal lipid accumulation that damages the kidneys’ filtration system, leading to kidney disease and its progression. VAR 200 passively and actively removes excess lipids from the kidney.
Preclinical studies in animal models of diabetic kidney disease, FSGS, and Alport syndrome, demonstrate that removal of excess cholesterol and lipids from the kidney’s filtration system with VAR 200 protects against structural damage and reduces excretion of protein in the urine (proteinuria). VAR 200 has potential to treat multiple kidney diseases, including diabetic kidney disease, and rare kidney diseases, FSGS (focal segmental glomerulosclerosis) and Alport syndrome. For more information about VAR 200, Click Here.
About ZyVersa Therapeutics, Inc.
ZyVersa is a clinical stage specialty biopharmaceutical company leveraging advanced, proprietary technologies to develop first-in-class drugs. Our focus is on patients with renal or inflammatory diseases who have significant unmet medical needs. Our development pipeline includes phase clinical stage Cholesterol Efflux MediatorTM VAR 200 in development to alleviate damaging accumulation of cholesterol and lipids in the filtering system of the kidneys. The lead indication is treatment of rare kidney disease, focal segmental glomerulosclerosis. VAR 200 has potential to treat other kidney diseases, including Alport syndrome and diabetic kidney disease. ZyVersa’s pipeline also includes proprietary inflammasome ASC inhibitor IC 100 that blocks initiation and perpetuation of damaging inflammation associated with a multitude of inflammatory diseases. IC 100 has potential to treat many different CNS and other inflammatory diseases. For more information, please visit www.zyversa.com.
Certain statements contained in this press release regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These include statements regarding management’s intentions, plans, beliefs, expectations, or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. ZyVersa Therapeutics, Inc (“ZyVersa”) uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions. Such forward-looking statements are based on ZyVersa’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including ZyVersa’s plans to develop and commercialize its product candidates, the timing of initiation of ZyVersa’s planned preclinical and clinical trials; the timing of the availability of data from ZyVersa’s preclinical and clinical trials; the timing of any planned investigational new drug application or new drug application; ZyVersa’s plans to research, develop, and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of ZyVersa’s product candidates; ZyVersa’s commercialization, marketing and manufacturing capabilities and strategy; ZyVersa’s ability to protect its intellectual property position; and ZyVersa’s estimates regarding future revenue, expenses, capital requirements and need for additional financing. A discussion of these and other factors, including risks and uncertainties with respect to ZyVersa, is set forth in ZyVersa’s filings with the Securities and Exchange Commission, including ZyVersa’s Annual Report on Form 10-K and its Quarterly Reports on Form 10-Q.
New factors emerge from time-to-time, and it is not possible for ZyVersa to predict all such factors, nor can ZyVersa assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements included in this press release are based on information available to ZyVersa as of the date of this press release. ZyVersa disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law.
Corporate and IR Contact Karen Cashmere Chief Commercial Officer kcashmere@zyversa.com 786-251-9641
Media Contacts Casey McDonald cmcdonald@tiberend.com 646-577-8520
Dave Schemelia Dschemelia@tiberend.com 609-468-9325
Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation. Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in a combination trial with estrogen blockade in advanced endometrial cancer. Based on preclinical and clinical studies of CDK 4/6 inhibitors, Onconova is also evaluating opportunities for combination studies with narazaciclib in additional indications. Onconova’s product candidate rigosertib is being studied in multiple investigator-sponsored studies. These studies include a dose-escalation and expansion Phase 1/2a study of oral rigosertib in combination with nivolumab in patients with KRAS+ non-small cell lung cancer, a Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC), and a Phase 2 trial evaluating rigosertib in combination with pembrolizumab in patients with metastatic melanoma.
Robert LeBoyer, Senior Vice President, Equity Research Analyst, Biotechnology, Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
Additional Presentations At Medical Meetings Show Broad Activity and Targeting. In the past week, Onconova has presented additional narazaciclib data at the American Society of Hematology (ASH) conference and the San Antonio Breast Cancer Symposium (SABCS). These presentations show broad multi-kinase activity, improved inhibition of tumor growth, and synergy with other drugs used in mantle cell lymphoma.
The Data Are Consistent With Earlier Presentations. The additional data details broad multi-kinase effects of narazaciclib. Comparisons with the three approved CDK4/6 inhibitors have shown narazaciclib stops cancer cell proliferation by inhibiting more targets and leads to potent, irreversible G1cell cycle blockade. Its side effect profile allows for daily dosing, rather than the 3-week dosing followed by a week of rest to allow recovery.
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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.
Pharma giant AstraZeneca (AZN) announced Monday that it will purchase clinical-stage biotech Icosavax (ICVX) for up to $1.1 billion to augment its pipeline of vaccines targeting respiratory illnesses. Specifically, AstraZeneca aims to leverage Icosavax’s innovative virus-like particle (VLP) platform to develop a first-in-class combination vaccine against respiratory syncytial virus (RSV) and human metapneumovirus (hMPV).
Icosavax’s novel VLP technology promises stronger efficacy, fewer side effects, and more durable protection than traditional vaccines – a potential game changer. And the biotech’s lead asset IVX-A12 delivered stellar phase 2 results earlier this year, prompting AstraZeneca to make this big bet on the future of infectious disease prevention.
Transformational Vaccine Approach
At the heart of this deal lies Icosavax’s VLP platform that engineers tiny proteins to mimic the structure of viruses and trigger a robust immune response. Think of VLPs as a sneaky way to train the body to fight off viruses without exposing it to any actual viral particles.
And the data so far indicates VLPs induce broader, more durable protection against infection than conventional vaccines. For example, the VLP approach is behind the extremely efficacious human papillomavirus and hepatitis B virus vaccines on the market today.
Icosavax builds on this proven concept with computationally designed VLPs targeting the unique antigens of RSV and hMPV. So AstraZeneca clearly coveted access to this next-generation technology that could change the way we immunize populations against common illness.
Expedited Path for Lead Asset
Central to the deal is Icosavax’s IVX-A12, a combo VLP vaccine to prevent RSV and hMPV, which both cause severe respiratory infection in the elderly and immunocompromised. IVX-A12 demonstrated outstanding immunogenicity – triggering enduring antibody responses – along with a clean safety profile in trials so far.
In fact, the vaccine’s phase 2 results were strong enough for the FDA to award IVX-A12 Fast Track designation. This promises an expedited path to approval given the high unmet need: there are no approved vaccines for older adults against these widespread, often dangerous pathogens.
So AstraZeneca leapfrogs development by 3-4 years via this acquisition rather than advancing an early-stage candidate itself. As part of a big pharma, IVX-A12 now has the resources for rapid phase 3 trials and submission for emergency use authorization potentially next year.
Aligns with Growth Strategy
Importantly, this deal fits squarely with AstraZeneca’s strategy of strengthening its portfolio in areas of high unmet need. As Executive VP Iskra Reic highlighted, adding IVX-A12 distinguishes AstraZeneca’s late-stage pipeline in preventative infectious disease treatments.
While the company already markets FluMist for influenza, a next-gen offering like IVX-A12 that could supplant outdated RSV vaccines or ineffective hMPV options would be a true differentiator. It also complements AstraZeneca’s leading COVID-19 antibody cocktail for immunocompromised patients unable to mount their own response.
Beyond the tech and pipeline boost, Icosavax also brings its experienced team and manufacturing capabilities to scale up production in anticipation of launch.
Investor Implications
Turning to the transaction itself, AstraZeneca’s upfront $15 per share offer in cash reflects a 43% premium to Icosavax’s December 9 close before rumors leaked. Including the $5 per share milestone payment, the total value exceeds $1 billion for a 91% premium.
Of course the back half requires IVX-A12 to gain approval and hit $750 million in sales, so some risk is baked in. But given peak revenue estimates exceeding $2 billion, this seems doable over 5-10 years post-launch.
Investors should watch for completion of the tender offer expected in Q1 2024. Passing majority shareholder approval should be straightforward with such a compelling premium. Then it becomes about execution – advancing IVX-A12 rapidly through late-stage trials.
Ultimately though, AstraZeneca makes a well-timed bet on revolutionary vaccine science that could elevate its infectious disease segment to new heights. And Icosavax investors get to participate in this next chapter via an up to 91% buyout windfall. Once again, merger mania in biopharma looks set to pay off handsomely.
Pharmaceutical giant Merck announced Tuesday that it will acquire Caraway Therapeutics, a preclinical biotech company pursuing novel approaches to treating genetically defined neurodegenerative and rare diseases. The deal reflects Merck’s ongoing commitment to developing much-needed disease-modifying therapies for progressive brain conditions.
Under the agreement, Merck will make an upfront payment to obtain Caraway, followed by additional milestone payments contingent upon the progress of certain Caraway pipeline assets. Though financial terms were not disclosed, the total potential consideration could reach up to $610 million.
“Caraway’s multidisciplinary approach has yielded important progress in evaluating novel mechanisms of modulation of lysosomal function with potential for the treatment of progressive neurodegenerative diseases,” said George Addona, Merck’s head of discovery. “We look forward to applying our expertise to build upon this work with the goal of developing much needed disease-modifying therapies for these conditions.”
Unlike symptomatic treatments, disease-modifying therapies aim to directly impact underlying disease processes and ultimately alter the course of a condition’s progression. This has remained an elusive goal for brain diseases like Alzheimer’s and Parkinson’s.
Caraway’s work targets dysfunctions in cellular “recycling” processes that clear toxic materials from the brain. Its treatments stimulate lysosomes, which act as cell disposal units, to boost their activity. Researchers believe a boost in waste clearance could counter neurodegeneration.
Merck has been an investor in Caraway since 2018 through its venture capital arm MRL Ventures Fund. Now, by folding Caraway’s team and portfolio into its research labs, Merck aims to leverage its considerable drug development capabilities to advance lysosomal modulation treatments for neurodegeneration.
“This is a testament to the hard work and dedication of the Caraway team and our mission to develop therapeutics with the potential to alter the progression of devastating neurodegenerative diseases and help patients,” said Caraway CEO Martin D. Williams in a statement. “This acquisition leverages Merck’s industry-leading research and development capabilities to help further advance our discovery and preclinical programs.”
Alongside Merck, Caraway has been backed by several high-profile life sciences investors including SV Health Investors, AbbVie Ventures, Amgen Ventures, and Eisai Innovation.
An Urgent Need for Better Brain Treatments
Currently available medications can only manage symptoms for a period of time for Alzheimer’s, Parkinson’s, and related neurodegenerative diseases. None treat underlying pathologies or substantially slow worsening cognition and functionality.
Alzheimer’s alone impacts more than 6 million Americans and the prevalence is expected to triple in the next 30 years if no new treatments emerge. Experts have emphasized the urgent need for innovations.
Major players in the pharmaceutical industry have confronted disappointed late-stage clinical trial results among proposed Alzheimer’s treatments over the past decade, suffering high-profile setbacks.
Yet Merck’s buy-in suggests promise still exists in Caraway’s early-stage lysosomal modulation approach, even though treatments haven’t advanced to human testing yet. Merck aims to apply its extensive expertise to push potential therapies over the finish line where others have stumbled before.
Continuing a Neuroscience Focus
Alongside this deal, Merck continues to expand its research across neurodegenerative diseases in other ways. Thus far in 2023, Merck has also entered into research collaborations to pursue non-amyloid targets for Alzheimer’s and chiral chemistry for better brain penetrance among compounds targeting neurological conditions.
“The alignment with Caraway’s innovative science and focus on elucidating disease-modifying neurotherapeutics dovetails nicely with our ongoing work,” said Addona.
Overall, Merck’s acquisition of Caraway signals both increasing momentum around emerging theories of neurodegeneration—like waste clearance’s role—and a formidable commitment by the pharma organization to translating the latest science into paradigm-shifting treatments for patients.
Q32 Bio, a clinical-stage biotech developing treatments for autoimmune and inflammatory diseases, announced it has entered into a definitive agreement to merge with Homology Medicines in an all-stock deal. The combined company will operate under the Q32 Bio name and focus on progressing Q32’s pipeline of novel immunomodulators.
Q32 is developing bempikibart (ADX-914), an anti-IL-7Rα antibody, as well as ADX-097, a tissue-targeted complement inhibitor. The merger will provide Q32 with access to public markets and additional capital to support the advancement of these programs through upcoming milestones.
Under the terms of the agreement, Homology Medicines shareholders will receive 25% ownership in the combined company, with Q32 shareholders owning 75%. The Board of Directors will consist of seven members from Q32 Bio and two from Homology Medicines. The companies expect the transaction to close in Q1 2024.
Regaining Worldwide Rights to Lead Candidate Bempikibart
Concurrent with the merger announcement, Q32 revealed that it has re-acquired full worldwide rights to bempikibart from Amgen. Q32 originally licensed bempikibart from Amgen in 2021 after the pharma giant took it through Phase 1 trials.
Bempikibart blocks signaling mediated by IL-7 and TSLP to modulate T cell-driven inflammation. It is currently being evaluated in two Phase 2 studies in atopic dermatitis and alopecia areata, with topline results expected in the second half of 2024.
Regaining full rights to bempikibart provides Q32 with greater control over the program’s development and commercial potential. The merger and additional funding will support pivotal studies to bring bempikibart to market.
Advancing Complement Inhibitor ADX-097 into the Clinic
In addition to bempikibart, Q32 is developing ADX-097 as an innovative approach to inhibiting complement activation for autoimmune and inflammatory disorders. Excessive complement activation is implicated in diseases like ANCA-associated vasculitis, IgA nephropathy, and NMOSD.
Unlike current complement drugs that cause systemic inhibition, ADX-097 is engineered to potently inhibit complement only in targeted tissues. This allows greater on-target activity with potentially improved safety.
Q32 recently completed a Phase 1 trial of ADX-097, demonstrating a favorable tolerability and immunogenicity profile. The company will now advance ADX-097 into Phase 2 testing, with initial proof-of-concept data expected by end of 2024 and topline results from two trials in 2H 2025.
Strengthening Financial Position to Reach Critical Milestones
To support its pipeline advancement, Q32 has secured a $42 million private placement in conjunction with the proposed merger. New and existing investors participated, including OrbiMed, Bristol Myers Squibb, Sanofi Ventures and others.
This additional capital will fund operations through several key milestones:
Phase 2 data for bempikibart in atopic dermatitis and alopecia areata in 2H 2024
Initial Phase 2 proof-of-concept data for ADX-097 by end of 2024
Topline Phase 2 results for ADX-097 in 2H 2025
The combined company is expected to have approximately $115 million in cash at closing, providing runway into mid-2026. This strengthened financial position will enable Q32 to reach meaningful catalysts for its lead programs.
Experienced Leadership to Drive Clinical Development
The combined immunology-focused company will be led by the Q32 Bio executive team, including:
Jodie Morrison, CEO
Shelia Violette, PhD, Founder and CSO
Jason Campagna, MD, PhD, CMO
Saul Fink, PhD, CTO
Maria Marzilli, MPH, EVP of Corporate Strategy & Operations
David Appugliese, JD, SVP, Head of People
Q32’s management has extensive experience leading R&D, corporate strategy, and operations at companies like Editas Medicine, Bioverativ, and Ironwood Pharmaceuticals.
Ms. Morrison commented, “The proposed merger with Homology Medicines and concurrent private placement is expected to provide Q32 Bio with the capital to drive development of our autoimmune and inflammatory pipeline through multiple clinical milestones. We look forward to delivering Phase 2 data for bempikibart and ADX-097 that could support the advancement of these programs toward commercialization.”
The transaction will provide Q32 Bio with the financial capacity and public listing to further advance its pipeline of novel immunology therapies for patients with autoimmune and inflammatory diseases. Shareholders of both companies will have the opportunity to realize future value if the combined pipeline progresses as planned.
Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation. Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in a combination trial with estrogen blockade in advanced endometrial cancer. Based on preclinical and clinical studies of CDK 4/6 inhibitors, Onconova is also evaluating opportunities for combination studies with narazaciclib in additional indications. Onconova’s product candidate rigosertib is being studied in multiple investigator-sponsored studies. These studies include a dose-escalation and expansion Phase 1/2a study of oral rigosertib in combination with nivolumab in patients with KRAS+ non-small cell lung cancer, a Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC), and a Phase 2 trial evaluating rigosertib in combination with pembrolizumab in patients with metastatic melanoma.
Robert LeBoyer, Senior Vice President, Equity Research Analyst, Biotechnology, Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
Clinical Milestones For Narazaciclib and Rigosertib Expected In 2024. Onconova reported a 3Q23 loss of $4.7 million or $(0.23) per share. Cash on hand at the end of the quarter was $25.2 million, which we believe is sufficient to fund operations through 3Q24. The company reviewed several recent data presentations and the clinical milestones ahead for 2024.
An Additional Dose Level Has Been Added To The Narazaciclib Phase 1/2 Study. As expected, Onconova announced that an additional dosing cohort has been added to the Phase 1/2 dose-escalation trial in solid tumors. The maximum tolerated dose (MTD) was not reached in the first 6 cohorts, and did not show neutropenia and diarrhea commonly seen in other CDK4/6 inhibitors. This allows a higher dose level to be tested. The Phase 1/2 trial is expected to continue into 1Q23, followed by Phase 2 dose selection.
Equity Research is available at no cost to Registered users of Channelchek. Not a Member? Click ‘Join’ to join the Channelchek Community. There is no cost to register, and we never collect credit card information.
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.
Topline Results from Phase 3 Potentially NDA-Enabling Study of TNX-102 SL in Fibromyalgia Expected Late December 2023: Centrally-Acting Non-Opioid Analgesic
Topline Results from Phase 2 Proof-of-Concept Study ofTNX-1900 in Chronic Migraine Expected Early December 2023: Intranasal Potentiated Oxytocin
Meaningful Progress Made in Obtaining External Support for Clinical Trials from U.S. Government Agencies and Other Institutions
Revenue from Marketed Acute Migraine Products: Zembrace® SymTouch® (sumatriptan injection) and Tosymra® (sumatriptan nasal spray) Included in Third Quarter Financial Statements
CHATHAM, N.J., Nov. 09, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline of development candidates, today announced financial results for the third quarter ended September 30, 2023, and provided an overview of recent operational highlights.
“Tonix expects topline results from its Phase 3 fibromyalgia study and Phase 2 chronic migraine study before year end,” said Seth Lederman, M.D., Chief Executive Officer of Tonix. “The Phase 3 RESILIENT trial in fibromyalgia, if successful, is expected to be the final efficacy trial required for submitting a New Drug Application (NDA) for approval by the U.S. Food and Drug Administration (FDA) for TNX-102 SL (cyclobenzaprine HCl sublingual tablets). In the Phase 2 proof-of-concept PREVENTION study in chronic migraine of TNX-1900 (intranasal potentiated oxytocin), all patients have completed their final visit and topline results are expected in early December 2023.”
Dr. Lederman continued, “We are continuing to shift the expense of clinical trials from our operating budget to U.S. government agencies and other institutions through partnerships. The U.S. Department of Defense (DoD) is supporting the upcoming Phase 2 study of TNX-102 SL in acute stress disorder, being conducted and sponsored by University of North Carolina (UNC). The U.S. National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID), through its Project NextGen, will conduct the Phase 1 study of our vaccine candidate TNX-1800 (modified recombinant horsepox virus, live vaccine). The National Institute of Drug Abuse (NIDA) is supporting our Phase 2 study of TNX-1300 (recombinant double mutant cocaine esterase) for cocaine intoxication. Massachusetts General Hospital (MGH) is conducting Phase 2 studies of TNX-1900 in binge eating disorder and pediatric obesity, and the University of Washington is conducting a Phase 2 study of TNX-1900 in social anxiety disorder. Finally, we continue to collaborate with MGH on several preclinical non-human primate studies for TNX-1500 (anti-CD40L Fc-modified humanized monoclonal antibody), currently in a Phase 1 study being conducted by Tonix. These outside collaborations leverage our internal resources and allow us to progress our clinical programs in a capital efficient manner.”
Partnerships with External Funding – Recent Highlights
NIH/NIAID selected Tonix’s vaccine candidate, TNX-1800, as part of Project NextGen; a Phase 1 study is expected to start in the second half of 2024. NIH/NIAID will cover the full cost of the clinical trial, while Tonix will supply the vaccine candidate.
NIDA is supporting a Phase 2 study on TNX-1300 for cocaine Intoxication; expected to start enrolling patients in the fourth quarter of 2023.
DoD is supporting a Phase 2 investigator-initiated study of TNX-102 SL for acute stress disorder at UNC for motor vehicle accident victims; expected to start enrolling patients in 2024.
MGH/Harvard Medical School is conducting Phase 2 investigator-initiated studies of TNX-1900 in binge eating disorder and adolescent obesity.
The University of Washington is conducting a Phase 2 investigator-initiated study of TNX-1900 in social anxiety disorder.
Marketed Products – Recent Highlights
In September 2023, Tonix announced that it is committed to meeting potential increased demand for Tosymra® (sumatriptan nasal spray) 10 mg after GlaxoSmithKline’s planned discontinuation of Imitrex® (sumatriptan) nasal spray 5 mg and 20 mg products after January 2024. Tonix is preparing for potential increased demand for Tosymra to help avoid possible drug shortages for patients who suffer from migraines. Tosymra nasal spray is approved on the basis of bioequivalence to Imitrex injection 4 mg.
Tonix completed the acquisition of Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra from Upsher-Smith Laboratories, LLC in June 2023. Both products are indicated for the treatment of acute migraine with or without aura in adults.
Key Product Candidates* — Recent Highlights
Central Nervous System (CNS) Pipeline
TNX-102 SL (cyclobenzaprine HCl sublingual tablets): once-daily at bedtime small molecule for the management of fibromyalgia (FM) – a centrally-acting, non-opioid analgesic.
The Company announced in August 2023 that it completed enrollment of its potentially confirmatory Phase 3 RESILIENT trial of TNX-102 SL 5.6 mg in FM. 457 participants were randomized in the trial, which, if successful, is expected to serve as the final, well-controlled efficacy trial required for submission of NDA for approval by the FDA. RESILIENT is a registration-quality, double-blind, placebo-controlled study. Topline results from the RESILIENT trial are expected in late December of 2023.
TNX-102 SL for the treatment of acute stress reaction (ARS) and acute stress disorder (ASD), and prophylaxis against development of posttraumatic stress disorder (PTSD)
In September 2023, the Company announced that the UNC Institute for Trauma Recovery has been awarded a $3 million grant from the DoD to investigate the potential of Tonix’s TNX-102 SL to reduce the frequency and severity of adverse effects of acute trauma, which include ASR and ASD, and development of PTSD. The proposed Phase 2, Optimizing Acute Stress Reaction Interventions with TNX-102 SL (OASIS) study will examine the safety and efficacy of TNX-102 SL to reduce adverse posttraumatic neuropsychiatric sequelae among patients presenting to the emergency department (ED) after a motor vehicle collision (MVC). The study will enroll approximately 180 MVC trauma survivors at ED study sites in the U.S. Participants will be randomized in the ED to receive a two-week course of either TNX-102 SL or placebo.
Initiation of patient enrollment in the proposed investigator-sponsored OASIS study is anticipated in the beginning of 2024, subject to clearance by the FDA of an investigator-initiated Investigational New Drug (IND) application.
TNX-102 SL for the treatment of Fibromyalgia-Type Long COVID, also known as Post-Acute Sequelae of COVID-19 (PASC)
In September 2023, the Company announced topline results from its Phase 2 PREVAIL proof-of-concept study of TNX-102 SL for fibromyalgia-type Long COVID. TNX-102 SL showed a robust Cohen’s d effect size of 0.5 in improving fatigue relative to placebo; and it showed consistent activity across secondary measures of sleep quality, cognitive function, disability and Patient Global Impression of Change, but did not meet the primary endpoint of multi-site pain reduction at week 14. TNX-102 SL was generally well tolerated and no new safety signals were observed.
The Company intends to request an End-of-Phase 2 meeting with the FDA to discuss a potential Phase 3 program based on a proposed primary outcome measure using the PROMIS Fatigue scale. The meeting is expected to take place in the first quarter of 2024.
TNX-1900 (intranasal potentiated oxytocin): small peptide for migraine, craniofacial pain, social anxiety disorder (SAD), insulin resistance and related disorders, and adolescent obesity and binge eating disorder
In October 2023, the Company announced it completed the clinical phase of the PREVENTION study, a Phase 2 proof-of-concept study of TNX-1900 for the prevention of migraine headaches in chronic migraineurs, as the last of 88 enrolled patients completed their final study visit. PREVENTION is a registration-quality, double-blind, placebo-controlled study.
Topline results from the PREVENTION Phase 2 trial are expected in early December 2023.
In September 2023, the Company announced that David C. Yeomans, Ph.D. presented data relevant to the proposed mechanism of TNX-1900 in treating chronic migraine in a poster and an oral presentation at the 2023 International Headache Congress (IHC) in Seoul, South Korea. The poster and oral presentation titled, “Human trigeminal ganglia possess oxytocin receptors on CGRP positive neurons: expression increased by inflammation,” include research sponsored by and licensed to Tonix. The presentations show that oxytocin receptors are co-expressed with calcitonin gene-related peptide (CGRP) on human trigeminal ganglia neurons, which is similar to Professor Yeomans’ previous findings in animal trigeminal ganglia. The inflammatory cytokine IL-6 upregulated expression of oxytocin receptors on human trigeminal neurons, consistent with the previously observed impact of inflammation on the potency of oxytocin on its receptor. In animals, oxytocin has been shown to functionally inhibit the excitability of trigeminal neurons, which is consistent with oxytocin inhibiting the release of CGRP at trigeminal nerve terminals.1
Tonix announced in July 2023 that the first participant was enrolled in the investigator-initiated Phase 2 STROBE Study of TNX-1900 for the treatment of binge-eating disorder at MGH. Tonix is supporting the STROBE study through a clinical trial agreement with MGH.
Tonix announced in July 2023 that the first participant was enrolled in a Phase 2 investigator-initiated, proof-of-concept study of TNX-1900 for enhancing social safety learning in SADSAD. Tonix entered into an agreement with the University of Washington to examine the potential role of TNX-1900 in enhancing vicarious extinction learning in SAD, compared to healthy controls.
Tonix announced in July 2023 that the first participant was enrolled in the Phase 2 POWER study of TNX-1900 for the treatment of pediatric obesity with MGH. MGH is the sponsor of the NIH-funded trial, being conducted under an investigator-initiated IND.
Tonix expects to initiate a Phase 2 clinical study of TNX-1300 for the treatment of cocaine intoxication in the fourth quarter of 2023. In 2022, Tonix was awarded a Cooperative Agreement grant from NIDA, part of the NIH, to support development of TNX-1300.
TNX-1300 has been granted Breakthrough Therapy designation by the FDA.
Rare Disease Pipeline
TNX-2900 (intranasal potentiated oxytocin): small peptide for the treatment of Prader-Willi syndrome (PWS)
In October 2023, Herbert Harris, M.D., Ph.D., Executive Vice President, Translational Medicine of Tonix Pharmaceuticals, provided an overview of Tonix’s TNX-2900 program at the Foundation for Prader-Willi Research (FPWR) Family Conference in Denver, CO. The presentation highlights preclinical data showing the enhancing effects of magnesium (Mg2+) on the activation of oxytocin receptors. The Mg2+ enhanced formulation of intranasal oxytocin is the basis for TNX-2900, in development to treat hyperphagia, or pathological over-eating, in children and adolescents with PWS. In preclinical studies, Mg2+ increases the potency of oxytocin, which is a peptide hormone that reduces appetite and signals fullness, potentially improving receptor binding and resulting in improved therapeutic action.
Immunology Pipeline
TNX-1500 (anti-CD40L Fc-modified humanized monoclonal antibody): third generation anti-CD40L monoclonal antibody for prophylaxis of organ transplant rejection and treatment of autoimmune disorders.
In October 2023, the Company announced data from two oral presentations which were delivered recently at the American College of Surgeons (ACS) Clinical Congress 2023, and The International Pancreas and Islet Transplant Association (IPITA), the International Xenotransplantation Association (IXA), and the Cell Transplant and Regenerative Medicine Society (CTRMS) Joint Congress by faculty at the Center for Transplantation Sciences, MGH. The oral presentations titled, “Pilot Evaluation of a Clinical Xeno Heart Transplant Regimen in a Preclinical Model” and “Extended Survival of 9- and 10-Gene Edited Pig Heart Xenografts with Ischemia Minimization and CD154 Costimulation Blockade-Based Immunosuppression” by Dr. Ikechukwu Ileka et al. include data demonstrating the use of TNX-1500 as maintenance therapy after xeno heart transplant in non-human primates. In both studies, genetically engineered (GE) pigs in baboon transplants were treated with cold-perfused ischemia minimization and a novel costimulation-based immunosuppressive regimen that includes TNX-1500.
In October 2023, Tonix announced that a study published in the Journal Nature2 by faculty at the Center for Transplantation Sciences, MGH in collaboration with biotechnology company, eGenesis, utilized TNX-1500 as part of the immune modulating regimen to prevent organ transplant rejection. The Nature article titled, “Design and testing of a humanized porcine donor for xenotransplantation” includes data that provide additional support for TNX-1500’s activity in preventing pig xenograft organ rejection and for its safety and tolerability in non-human primates.
In August 2023, Tonix announced the initiation of a Phase 1 single ascending dose study of TNX-1500 in healthy volunteers. The primary objectives of the study are to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous TNX-1500. This first-in-human study is intended to support dosing in a planned Phase 2 trial in kidney transplant recipients.
The first indication for TNX-1500 will be prophylaxis of organ rejection in adult patients receiving a kidney transplant, but multiple additional indications are possible, including autoimmune diseases. Two peer reviewed publications described the work at the MGH on allogeneic transplants in animals were published.3,4
Infectious Disease Pipeline
TNX-1800 (modified recombinant horsepox virus, live vaccine): potential vaccine to protect against COVID-19 designed to express the SARS-CoV-2 spike protein
In November 2023, Tonix announced that NIAID, a part of the NIH, will conduct a Phase 1 clinical trial with TNX-1800 as part of Project NextGen. The Phase 1 trial of TNX-1800 is expected to start in the second half of 2024. NIAID will cover the full cost of the clinical trial, including operations and related analyses. Tonix will be responsible for providing clinical trial materials, and upon completion will have the right to rely on the findings in regulatory filings with the FDA to support the approval of its COVID-19 vaccine and other vaccines based on the RPV platform.
TNX-801 (recombinant horsepox virus, live vaccine): potential vaccine to protect against mpox disease and smallpox.
In August 2023, Tonix received the official written response from a Type B pre-IND meeting with the FDA to develop TNX-801 as a potential vaccine to protect against mpox disease (formerly known as monkeypox) and smallpox. Tonix believes the FDA feedback provides a path to agreement on the design of a Phase 1/2 study and the overall clinical development plan. The Phase 1/2 clinical trial will assess the safety, tolerability, and immunogenicity of TNX-801, following the submission and clearance of an IND.
*All of Tonix’s product candidates are investigational new drugs or biologics and none have been approved for any indication.
1Tzabazis A, et al. Cephalalgia. 2016. 36(10):943-50.
2Anand R.P., et al. Nature. 2023. 622, 393–401.
3Lassiter, G., et al. (2023). TNX-1500, a crystallizable fragment–modified anti-CD154 antibody, prolongs non-human primate renal allograft survival. American Journal of Transplantation. https://doi.org/10.1016/j.ajt.2023.03.022
4Miura, S., et al. (2023). TNX-1500, a crystallizable fragment–modified anti-CD154 antibody, prolongs non-human primate cardiac allograft survival. American Journal of Transplantation. https://doi.org/10.1016/j.ajt.2023.03.025
Recent Highlights—Financial
As of September 30, 2023, Tonix had approximately $6.9 million of cash and cash equivalents, compared to $120.2 million as of December 31, 2022. Additionally, Tonix had inventory totaling approximately $13.3 million as of September 30, 2023. In August 2023, Tonix received net proceeds of approximately $6.3 million through a public offering of common stock, after deducting underwriting discount and other offering expenses. Cash used in operations was approximately $79.7 million for the nine months ended September 30, 2023, compared to $75.8 million for the same period in 2022. Cash used by investing activities for the nine months ended September 30, 2023 was approximately $28.6 million.
On September 28, 2023, the Company sold 4,050,000 shares of common stock, pre-funded warrants to purchase up to 4,950,000 shares of common stock, and accompanying common A warrants to purchase 9,000,000 shares of common stock and common B warrants to purchase up to 9,000,000 shares of common stock in a public offering for net proceeds of approximately $4.0 million, after deducting underwriting discount and other offering expenses. This public offering closed on October 3, 2023.
Third Quarter 2023 Financial Results
Net product revenue for the third quarter 2023 was approximately $4.0 million. As a reminder, Tonix completed the acquisition of two currently marketed products from Upsher-Smith Laboratories, LLC on June 30, 2023.
During the three months ended September 30, 2023, Tonix received $0.4 million from NIDA for the TNX-1300 study to treat cocaine intoxication.
R&D expenses for the third quarter 2023 were approximately $21.1 million, compared to $22.2 million for the same period in 2022. This decrease is predominantly due to decreased non-clinical and manufacturing expenses, offset by an increase in clinical, employee-related and professional expenses.
SG&A expenses for the third quarter 2023 were $8.7 million, compared to $7.4 million for the same period in 2022. The increase was primarily due to sales and marketing associated with the Company’s recently acquired marketed products.
Net loss available to common stockholders was $28.0 million, or $1.83 per share, basic and diluted, for the third quarter 2023, compared to net loss available to common stockholders of $29.0 million, or $4.24 per share, basic and diluted, for the same period in 2022. The basic and diluted weighted average common shares outstanding for the third quarter 2023 was 15,327,558 compared to 6,843,099 shares for the same period in 2022.
Tonix Pharmaceuticals Holding Corp.*
Tonix is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary, markets Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith Laboratories, LLC from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment of acute migraine with or without aura in adults. Tonix’s development portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS development portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead development CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in late December 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition, and topline results were reported in the third quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), is in development as a preventive treatment in chronic migraine, and enrollment has completed in a Phase 2 proof-of-concept study with topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and social anxiety disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the fourth quarter of 2023. Tonix’s rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology development portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix’s infectious disease pipeline includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant pox vaccine platform for other infectious diseases, including TNX-1800, in development as a vaccine to protect against COVID-19. During the fourth quarter of 2023, TNX-1800 was selected by the U.S. National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) Project NextGen for inclusion in Phase 1 clinical trials. The infectious disease development portfolio also includes TNX-3900 and TNX-4000, which are classes of broad-spectrum small molecule oral antivirals.
*Tonix’s product development candidates are investigational new drugs or biologics and have not been approved for any indication.
Zembrace SymTouch and Tosymra are registered trademarks of Tonix Medicines. Intravail is a registered trademark of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis, Inc. All other marks are property of their respective owners.
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 failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the failure to successfully market any of our products; 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, 2022, as filed with the Securities and Exchange Commission (the “SEC”) on March 13, 2023, 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.
TONIX PHARMACEUTICALS HOLDING CORP.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(In Thousands, Except Share and Per Share Amounts)
(unaudited)
Three Months Ended September 30,
Nine Months Ended September 30,
2023
2022
2023
2022
REVENUE:
Product revenue, net
$
3,989
$
—
$
3,989
$
—
COSTS AND EXPENSES:
Cost of revenue
$
2,374
$
—
$
2,374
$
—
Research and development
21,050
22,201
69,537
57,202
Selling, general and administrative
8,712
7,390
23,129
22,161
32,136
29,591
95,040
79,363
Operating loss
(28,147
)
(29,591
)
(91,051
)
(79,363
)
Interest income, net
172
610
1,715
825
Net loss
(27,975
)
(28,981
)
(89,336
)
(78,538
)
Preferred stock deemed dividend
—
—
—
4,255
Net loss available to common stockholders
$
(27,975
)
$
(28,981
)
$
(89,336
)
$
(82,793
)
Net loss per common share, basic and diluted
$
(1.83
)
$
(4.24
)
$
(7.40
)
$
(18.58
)
Weighted average common shares outstanding, basic and diluted
15,327,558
6,843,099
12,079,583
4,455,943
See the accompanying notes to the condensed consolidated financial statements
TONIX PHARMACEUTICALS HOLDING CORP.
CONDENSED CONSOLIDATED BALANCE SHEETS
(In Thousands)
(Unaudited)
September 30, 2023
December 31, 20221
Assets
Cash and cash equivalents
$
6,914
$
120,229
Inventory
13,317
–
Receivables, net
1,562
–
Prepaid expenses and other
9,544
10,548
Total current assets
31,337
130,777
Other non-current assets
107,945
94,913
Total assets
$
139,282
$
225,690
Liabilities and stockholders’ equity
Total liabilities
$
18,449
$
18,508
Stockholders’ equity
120,833
207,182
Total liabilities and stockholders’ equity
$
139,282
$
225,690
1The condensed consolidated balance sheet for the year ended December 31, 2022 has been derived from the audited financial statements but do not include all of the information and footnotes required by accounting principles generally accepted in the United States for complete financial statements.
Zembrace® SymTouch® (sumatriptan Injection): IMPORTANT SAFETY INFORMATION
Zembrace SymTouch (Zembrace) can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop use and get emergency help if you have any signs of a heart attack:
discomfort in the center of your chest that lasts for more than a few minutes or goes away and comes back
severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
pain or discomfort in your arms, back, neck, jaw or stomach
shortness of breath with or without chest discomfort
breaking out in a cold sweat
nausea or vomiting
feeling lightheaded
Zembrace is not for people with risk factors for heart disease (high blood pressure or cholesterol, smoking, overweight, diabetes, family history of heart disease) unless a heart exam shows no problem.
Do not use Zembrace if you have:
history of heart problems
narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease)
uncontrolled high blood pressure
hemiplegic or basilar migraines. If you are not sure if you have these, ask your provider.
had a stroke, transient ischemic attacks (TIAs), or problems with blood circulation
severe liver problems
taken any of the following medicines in the last 24 hours: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, ergotamines, dihydroergotamine.
are taking certain antidepressants, known as monoamine oxidase (MAO)-A inhibitors or it has been 2 weeks or less since you stopped taking a MAO-A inhibitor. Ask your provider for a list of these medicines if you are not sure.
an allergy to sumatriptan or any of the components of Zembrace
Tell your provider about all of your medical conditions and medicines you take, including vitamins and supplements.
Zembrace can cause dizziness, weakness, or drowsiness. If so, do not drive a car, use machinery, or do anything where you need to be alert.
Zembrace may cause serious side effects including:
changes in color or sensation in your fingers and toes
sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrhea, fever
cramping and pain in your legs or hips; feeling of heaviness or tightness in your leg muscles; burning or aching pain in your feet or toes while resting; numbness, tingling, or weakness in your legs; cold feeling or color changes in one or both legs or feet
increased blood pressure including a sudden severe increase even if you have no history of high blood pressure
medication overuse headaches from using migraine medicine for 10 or more days each month. If your headaches get worse, call your provider.
serotonin syndrome, a rare but serious problem that can happen in people using Zembrace, especially when used with anti-depressant medicines called SSRIs or SNRIs. Call your provider right away if you have: mental changes such as seeing things that are not there (hallucinations), agitation, or coma; fast heartbeat; changes in blood pressure; high body temperature; tight muscles; or trouble walking.
hives (itchy bumps); swelling of your tongue, mouth, or throat
seizures even in people who have never had seizures before
The most common side effects of Zembrace include: pain and redness at injection site; tingling or numbness in your fingers or toes; dizziness; warm, hot, burning feeling to your face (flushing); discomfort or stiffness in your neck; feeling weak, drowsy, or tired.
Tell your provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of Zembrace. For more information, ask your provider.
This is the most important information to know about Zembrace but is not comprehensive. For more information, talk to your provider and read the Patient Information and Instructions for Use. You can also visit www.upsher-smith.com or call 1-888-650-3789.
You are encouraged to report adverse effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
INDICATION AND USAGE
Zembrace is a prescription medicine used to treat acute migraine headaches with or without aura in adults who have been diagnosed with migraine.
Zembrace is not used to prevent migraines. It is not known if it is safe and effective in children under 18 years of age.
Tosymra can cause serious side effects, including heart attack and other heart problems, which may lead to death. Stop Tosymra and get emergency medical help if you have any signs of heart attack:
discomfort in the center of your chest that lasts for more than a few minutes or goes away and comes back
severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw
pain or discomfort in your arms, back, neck, jaw, or stomach
shortness of breath with or without chest discomfort
breaking out in a cold sweat
nausea or vomiting
feeling lightheaded
Tosymra is not for people with risk factors for heart disease (high blood pressure or cholesterol, smoking, overweight, diabetes, family history of heart disease) unless a heart exam is done and shows no problem.
Do not use Tosymra if you have:
history of heart problems
narrowing of blood vessels to your legs, arms, stomach, or kidney (peripheral vascular disease)
uncontrolled high blood pressure
severe liver problems
hemiplegic or basilar migraines. If you are not sure if you have these, ask your healthcare provider.
had a stroke, transient ischemic attacks (TIAs), or problems with blood circulation
taken any of the following medicines in the last 24 hours: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, ergotamines, or dihydroergotamine. Ask your provider if you are not sure if your medicine is listed above.
are taking certain antidepressants, known as monoamine oxidase (MAO)-A inhibitors or it has been 2 weeks or less since you stopped taking a MAO-A inhibitor. Ask your provider for a list of these medicines if you are not sure.
an allergy to sumatriptan or any ingredient in Tosymra
Tell your provider about all of your medical conditions and medicines you take, including vitamins and supplements.
Tosymra can cause dizziness, weakness, or drowsiness. If so, do not drive a car, use machinery, or do anything where you need to be alert.
Tosymra may cause serious side effects including:
changes in color or sensation in your fingers and toes
sudden or severe stomach pain, stomach pain after meals, weight loss, nausea or vomiting, constipation or diarrhea, bloody diarrhea, fever
cramping and pain in your legs or hips, feeling of heaviness or tightness in your leg muscles, burning or aching pain in your feet or toes while resting, numbness, tingling, or weakness in your legs, cold feeling or color changes in one or both legs or feet
increased blood pressure including a sudden severe increase even if you have no history of high blood pressure
medication overuse headaches from using migraine medicine for 10 or more days each month. If your headaches get worse, call your provider.
serotonin syndrome, a rare but serious problem that can happen in people using Tosymra, especially when used with anti-depressant medicines called SSRIs or SNRIs. Call your provider right away if you have: mental changes such as seeing things that are not there (hallucinations), agitation, or coma; fast heartbeat; changes in blood pressure; high body temperature; tight muscles; or trouble walking.
hives (itchy bumps); swelling of your tongue, mouth, or throat
seizures even in people who have never had seizures before
The most common side effects of Tosymra include: tingling, dizziness, feeling warm or hot, burning feeling, feeling of heaviness, feeling of pressure, flushing, feeling of tightness, numbness, application site (nasal) reactions, abnormal taste, and throat irritation.
Tell your provider if you have any side effect that bothers you or does not go away. These are not all the possible side effects of Tosymra. For more information, ask your provider.
This is the most important information to know about Tosymra but is not comprehensive. For more information, talk to your provider and read the Patient Information and Instructions for Use. You can also visit www.upsher-smith.com or call 1-888-650-3789.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
INDICATION AND USAGE Tosymra is a prescription medicine used to treat acute migraine headaches with or without aura in adults.
Tosymra is not used to treat other types of headaches such as hemiplegic or basilar migraines or cluster headaches.
Tosymra is not used to prevent migraines. It is not known if Tosymra is safe and effective in children under 18 years of age.
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract affecting 1 in 100 Americans (around 2.4 million people) that can lead to disabling bowel symptoms and progressive bowel damage.
Study provides direct evidence that NLRP3 signaling is over-activated in IBD, and that its inhibition attenuates intestinal inflammation and tissue damage, leading to significant improvements in IBD symptoms, and restoration of normal intestinal microbial flora.
ZyVersa is developing Inflammasome ASC Inhibitor IC 100 which can inhibit up to 12 different inflammasomes (including NLRP3 inflammasomes) and their associated ASC specks which perpetuate damaging inflammation.
WESTON, Fla., Nov. 09, 2023 (GLOBE NEWSWIRE) — ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA, or “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of inflammatory and renal diseases, announces publication of an article in the peer-reviewed Biomedical Journal demonstrating that inhibiting NLRP3 inflammasomes in an IBD animal model attenuates intestinal inflammation and tissue damage, leading to significant improvements in IBD symptoms, and restoration of normal intestinal microbial flora.
In the paper titled, “Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation,” the authors evaluated human colon biopsy samples from patients with IBD and healthy controls, and conducted a study in an IBD mouse model. Following are key findings reported in the paper:
NLRP3 and IL-1β expression is increased in the colon of IBD patients.
NLRP3 inhibition in the IBD animal model:
Inhibited NLRP3 inflammasome signaling in the colon, resulting in significantly reduced levels of the pro-inflammatory cytokines IL-1b, IL-6, and TNF-α.
Alleviated severe diarrhea and significantly improved IBD symptoms, based on the disease activity index score.
Attenuated histopathological changes indicative of tissue damage (goblet cell reduction, crypt destruction, and epithelial barrier disruption).
Restored gut microbiota to normal.
The authors stated, “In conclusion, this study provides direct evidence that NLRP3 signaling is over-activated in IBD patients. The inhibition of NLRP3 reverses the IBD-like symptoms in DSS-induced mice, which the regulatory effects on gut microbiota might mediate. Overall, this present study provides a basis for the clinical application of NLRP3 as a target for IBD treatment.” To read the article, Click Here.
“Restoration of quality of life is the ultimate long-term goal in IBD management. Although disease remission can often be achieved with current therapies, bothersome symptoms can still prevail,” stated Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO and President. “The research published in the Biomedical Journal provides support for inflammasome inhibition as a promising treatment option for IBD. ZyVersa is developing Inflammasome ASC inhibitor IC 100. Unlike NLRP3 inhibitors, designed to inhibit formation of one inflammasome to block initiation of the inflammatory cascade, IC 100 was designed to inhibit multiple types of inflammasomes and their associated ASC specks to uniquely block both initiation and perpetuation of damaging inflammation, which we believe is necessary to control chronic inflammation.” To review a white paper summarizing the mechanism of action and preclinical data for IC 100, Click Here.
About Inflammasome ASC Inhibitor IC 100
IC 100 is a novel humanized IgG4 monoclonal antibody that inhibits the inflammasome adaptor protein ASC. IC 100 was designed to attenuate both initiation and perpetuation of the inflammatory response. It does so by binding to a specific region of the ASC component of multiple types of inflammasomes, including NLRP1, NLRP2, NLRP3, NLRC4, AIM2, Pyrin. Intracellularly, IC 100 binds to ASC monomers, inhibiting inflammasome formation, thereby blocking activation of IL-1β early in the inflammatory cascade. IC 100 also binds to ASC in ASC Specks, both intracellularly and extracellularly, further blocking activation of IL-1β and the perpetuation of the inflammatory response that is pathogenic in inflammatory diseases. Because active cytokines amplify adaptive immunity through various mechanisms, IC 100, by attenuating cytokine activation, also attenuates the adaptive immune response.
About ZyVersa Therapeutics, Inc.
ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced, proprietary technologies to develop first-in-class drugs for patients with renal and inflammatory diseases who have significant unmet medical needs. The Company is currently advancing a therapeutic development pipeline with multiple programs built around its two proprietary technologies – Cholesterol Efflux Mediator™ VAR 200 for treatment of kidney diseases, and Inflammasome ASC Inhibitor IC 100, targeting damaging inflammation associated with numerous CNS and other inflammatory diseases. For more information, please visit www.zyversa.com.
Certain statements contained in this press release regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These include statements regarding management’s intentions, plans, beliefs, expectations, or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. ZyVersa Therapeutics, Inc (“ZyVersa”) uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions. Such forward-looking statements are based on ZyVersa’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including ZyVersa’s plans to develop and commercialize its product candidates, the timing of initiation of ZyVersa’s planned preclinical and clinical trials; the timing of the availability of data from ZyVersa’s preclinical and clinical trials; the timing of any planned investigational new drug application or new drug application; ZyVersa’s plans to research, develop, and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of ZyVersa’s product candidates; ZyVersa’s commercialization, marketing and manufacturing capabilities and strategy; ZyVersa’s ability to protect its intellectual property position; and ZyVersa’s estimates regarding future revenue, expenses, capital requirements and need for additional financing.
New factors emerge from time-to-time, and it is not possible for ZyVersa to predict all such factors, nor can ZyVersa assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements included in this press release are based on information available to ZyVersa as of the date of this press release. ZyVersa disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law.
This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any securities.
Corporate and IR Contact: Karen Cashmere Chief Commercial Officer kcashmere@zyversa.com 786-251-9641
Despite decades of effective environmental policy and improved air quality in the US, air pollution remains the greatest environmental health risk factor, contributing to 100,000 to 200,000 incremental deaths annually, primarily from fine particulate matter (PM2.5) derived from pollutants including vehicle and industrial emissions from fuel and biomasscombustion, cigarette smoke, volcanos, fires, and desert dust.
PM2.5 is inhaled into the lungs, spreading through the bloodstream to other organs, especially the kidney, which accumulates it during glomerular filtration, where it triggers NLRP3 inflammasome activation resulting in damaging inflammation and cell death (pyroptosis) leading to chronic kidney disease and its progression.
ZyVersa is developing Inflammasome ASC Inhibitor IC 100 which can inhibit up to 12 different inflammasomes (including NLRP3 inflammasomes) and their associated ASC specks which perpetuate damaging inflammation.
WESTON, Fla., Nov. 06, 2023 (GLOBE NEWSWIRE) — ZyVersa Therapeutics, Inc. (Nasdaq: ZVSA, or “ZyVersa”), a clinical stage specialty biopharmaceutical company developing first-in-class drugs for treatment of inflammatory and renal diseases, announces publication of an article in the peer-reviewed journal, Ecotoxicology and Environmental Safety, demonstrating that inhibiting NLRP3 inflammasomes can attenuate kidney damage and dysfunction associated with the environmental pollutant, PM2.5.
In the paper titled, “PM2.5 induces renal tubular injury by activating NLRP3-mediated pyroptosis,” the authors conducted studies in a mouse model exposed to high concentrations of ambient PM2.5 for 12 weeks, and in a mouse kidney cell line. Following are key findings reported in the paper:
PM2.5 exposure leads to kidney structural changes and functional impairment.
Inflammasome NLRP3-induced Inflammation and pyroptosis were increased in PM2.5-exposed kidney tissues.
Inhibiting the inflammasome NLRP3 pathway, including downstream caspase-1, rescued the kidneys from PM2.5-induced cell death.
The authors stated, “We further provided evidence that NLRP3-mediated pyroptosis plays critical roles in the progression of kidney injury induced by PM2.5 exposure. Inhibiting the activation of NLRP3 inflammasome can remarkably protect the renal tubular epithelial cells from PM2.5-induced proptosis.” To read the article, Click Here.
“The research published in the Journal,Ecotoxicology and Environmental Safety, reinforces other published data demonstrating that inhibiting NLRP3 inflammasomes can attenuate kidney damage and dysfunction of multiple causes, now including kidney damage associated with the environmental pollutant, PM2.5,” commented Stephen C. Glover, ZyVersa’s Co-founder, Chairman, CEO and President. “This research provides increasing support for inflammasome inhibition as a promising treatment option for kidney disease, a major health problem affecting over 35 million adults in the United States. ZyVersa is developing Inflammasome ASC inhibitor IC 100. Unlike NLRP3 inhibitors, designed to inhibit formation of one inflammasome to block initiation of the inflammatory cascade, IC 100 was designed to inhibit multiple types of inflammasomes and their associated ASC specks to uniquely block both initiation and perpetuation of damaging inflammation.” To review a white paper summarizing the mechanism of action and preclinical data for IC 100, Click Here.
About Inflammasome ASC Inhibitor IC 100
IC 100 is a novel humanized IgG4 monoclonal antibody that inhibits the inflammasome adaptor protein ASC. IC 100 was designed to attenuate both initiation and perpetuation of the inflammatory response. It does so by binding to a specific region of the ASC component of multiple types of inflammasomes, including NLRP1, NLRP2, NLRP3, NLRC4, AIM2, Pyrin. Intracellularly, IC 100 binds to ASC monomers, inhibiting inflammasome formation, thereby blocking activation of IL-1β early in the inflammatory cascade. IC 100 also binds to ASC in ASC Specks, both intracellularly and extracellularly, further blocking activation of IL-1β and the perpetuation of the inflammatory response that is pathogenic in inflammatory diseases. Because active cytokines amplify adaptive immunity through various mechanisms, IC 100, by attenuating cytokine activation, also attenuates the adaptive immune response.
About ZyVersa Therapeutics, Inc.
ZyVersa (Nasdaq: ZVSA) is a clinical stage specialty biopharmaceutical company leveraging advanced, proprietary technologies to develop first-in-class drugs for patients with renal and inflammatory diseases who have significant unmet medical needs. The Company is currently advancing a therapeutic development pipeline with multiple programs built around its two proprietary technologies – Cholesterol Efflux Mediator™ VAR 200 for treatment of kidney diseases, and Inflammasome ASC Inhibitor IC 100, targeting damaging inflammation associated with numerous CNS and other inflammatory diseases. For more information, please visit www.zyversa.com.
Certain statements contained in this press release regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These include statements regarding management’s intentions, plans, beliefs, expectations, or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. ZyVersa Therapeutics, Inc (“ZyVersa”) uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions. Such forward-looking statements are based on ZyVersa’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including ZyVersa’s plans to develop and commercialize its product candidates, the timing of initiation of ZyVersa’s planned preclinical and clinical trials; the timing of the availability of data from ZyVersa’s preclinical and clinical trials; the timing of any planned investigational new drug application or new drug application; ZyVersa’s plans to research, develop, and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of ZyVersa’s product candidates; ZyVersa’s commercialization, marketing and manufacturing capabilities and strategy; ZyVersa’s ability to protect its intellectual property position; and ZyVersa’s estimates regarding future revenue, expenses, capital requirements and need for additional financing.
New factors emerge from time-to-time, and it is not possible for ZyVersa to predict all such factors, nor can ZyVersa assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements included in this press release are based on information available to ZyVersa as of the date of this press release. ZyVersa disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law.
This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any securities.
Corporate and IR Contact: Karen Cashmere Chief Commercial Officer kcashmere@zyversa.com 786-251-9641
