Category: Health

What is CBD, and why am I seeing it everywhere?

(Note: companies that could be impacted by the content of this article are listed at the base of the story (desktop version). This article uses third-party references to provide a bullish, bearish and balanced point of view; sources listed in the “Balanced” section)

The widespread appeal of cannabidiol (CBD) in both consumer and medical markets is perhaps one of the most exciting developments to arise from the international trend toward cannabis legalization. The rapid rise in the popularity of CBD has encouraged companies across disparate industries to add it to their products. From cupcakes to beer to sunscreen to pet food, it seems that shoppers can now find CBD in almost anything. CBD has primarily been marketed as a treatment for anxiety relief and inflammation reduction, but there are claims that the supplement can treat many other disorders. The jury remains out on what CBD can actually do, but given CBD’s recent success it seems consumers are eager to experiment and find out.

Triple Technology to Engineer a Potent Anti-cancer Weapon, Part 3

(Note: companies that could be impacted by the content of this article are listed at the base of the story (desktop version). This article uses third-party references to provide a bullish, bearish and balanced point of view; sources listed in the “Balanced” section)

(click here for Part
1 or Part
2)

Medical breakthroughs usually occur when science and industry collide through combinations of various disciplines. Right now, we are on the verge of witnessing a potential medical breakthrough for the treatment of cancer as three discoveries converge:

1. Invention of CAR-T (Carl June, a scientist from University of Pennsylvania, pioneered CAR-T technology. Dr. June started treating cancer patients with it in 2010. In 2017, U.S. FDA approved the first two CAR-T medicines for the treatment of blood cancers)
2. Introduction of Checkpoint
   Inhibitors (Bristol-Myers’s Opdivo and Merck’s Keytruda were approved by FDA for the treatment of cancer in 2014/2016, respectively. Since then, the agency has approved these medicines for the treatment of various types of cancer)
3. Discovery of CRISP-Cas9 gene
   editing (In 2012, Jennifer Doudna, Emmanuelle Charpentier and Feng Zhang were credited for this eureka moment, as these scientists independently discovered CRISPR-Cas9 technology and predicted its significant potential. Jennifer (University of California, San Francisco), Emmanuelle Charpentier (Max Planck Institute) and Feng Zhang (Massachusetts Institute of Technology, MIT) were the inventors, respectively, of the technologies given rise to three emerging biotech companies: Intellia Therapeutics, CRISPR Therapeutics and Editas Medicine).

“Chimeric Antigen Receptor T cell therapy” (CAR-T) is a gene therapy designed to harness the potency of antibodies and T-lymphocytes into one single medicine for the treatment of cancer. CAR-T therapy could be viewed as a “living anti-cancer drug” as the medicine itself consists of a living cell, which is genetically engineered as a pharmaceutical “chimera” to find and destroy cancer cells (see Parts 1/2 of these series). Gene editing tools, such as CRISPR-Cas9, could be utilized to generate more effective CAR-T medicines (Figure 1).

Figure 1. Gene editing to engineer a “CAR-T
medicine”. 

 

 

 

 

 

 

 

Source: “T-cell tweaks to target tumors”. Nature 2017, 543:48-49

1. Traditional CAR-T Design. Traditional CARs (shown in yellow) are inserted at a random location into the genome (DNA) of T cells. If the CAR-T is expressed constitutively (constant synthesis), the cells often enter a state called “exhaustion” (become inactive). 
2. Use of CRISPR-Cas9. Gene-editing tool CRISPR–Cas9 used to replace the cell’s TCR-encoding gene (TCR – “natural T-cell receptor”, shown in green) with a CAR-T encoding sequence (shown in yellow). 
3. Gene-edited CAR-T. CRISPR–Cas9-edited T cells express only one type of TCR, the CAR-T (shown in yellow and red), providing better anti-tumor responses than traditional CAR T cells. The natural TCR (green) has been removed.

Click here to read Part 1 or Part 2 of this series on the revolutionary advances happening in the science of cancer treatment.

Thursday, July 25, 2019

Onconova Therapeutics (ONTX)

Once Fall, Twice Stand Up

Onconova Therapeutics, Inc., a clinical-stage biopharmaceutical company, focused on discovering and developing small molecule inhibitors to treat cancer. The lead product candidate rigosertib is in Phase 3 clinical trial for patients with higher risk myelodysplastic syndromes (MDS).

Ahu Demir, Biotechnology Research Analyst, Noble Capital Markets, Inc.

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

• Onconova’s main focus is MDS. Onconova Therapeutics is currently focused on completing a Phase 3 study (INSPIRE) with rigosertib, a RAS pathway inhibitor, for the treatment of 2nd line high-risk myelodysplastic syndrome (HR-MDS). MDS is a blood disorder caused by malfunctioning of the bone marrow, which fails to make enough normal blood cells. In March 2019, the company achieved 75 percent completion of patient enrollment. Full enrolment is expected in H2 2019, data readout to follow in 2020.
• Clinical Benefit in Selected Patient Population. Onconova’s Phase 3 clinical trial (ONTIME) showed lackluster survival benefit in HR-MDS patients based on data readout in 2014. However, post-hoc analysis of the data suggested…
  
  
  

  
  

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Tuesday, July 23, 2019

ProMIS Neurosciences (PMN:CA)

Amid Skepticism, Light Will Emerge in Alzheimer’s Area

ProMIS Neurosciences, Inc., a development stage biotech company, discovers and develops precision medicine therapeutics for the treatment of neurodegenerative diseases, primarily Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS).

Cosme Ordonez, MD, Ph.D., Senior Life Sciences Analyst, Noble Capital Markets, Inc.

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

• ProMIS showcases its technology at Medical Conference. At the Annual Alzheimer’s Association International Conference (AAIC) held in Los Angeles last week, Dr. Johanne Kaplan, the company’s Chief Development Officer, made an oral presentation on the therapeutic potential of candidate drug PMN310 for the treatment of Alzheimer’s disease (AD).
  
• Despite current skepticism, there is still hope. In recent months, negative news released by…
  
  
  

  
  

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NOTE: investment decisions should not be based upon the content of
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making any investment decision. 

Wednesday, July 10, 2019

Trovagene Inc. (TROV)

What does Colorectal Cancer Trial Add?

TrovaGene Inc is a US-based life science company which focuses on the development and commercialization of a proprietary molecular genetic detection technology for use in pharmaceutical development, clinical research and medical testing across a variety of clinical disciplines, including oncology and virology.    

Ahu Demir, Ph.D., Biotechnology Research Analyst, Noble Capital Markets, Inc.

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

• Colorectal cancer is the third active clinical trial assessing Onvansertib.. Trovagene initiated patient enrollment in a Phase 1b/2 clinical trial for the treatment of KRAS-mutated metastatic colorectal cancer (mCRC) on July 9, 2019. In addition to this trial, Trovagene is currently evaluating Onvansertib in a Phase 1b/2 study of acute myeloid leukemia (AML), and in a Phase 2 trial of metastatic castration-resistant prostate cancer (mCRPC).
• Unfulfilled need in colorectal cancer treatment.. Among the three cancer types targeted by Onvansertib, colorectal cancer represents the largest… 

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NOTE: investment decisions should not be based upon the content of
this research summary.  Proper due diligence is required before
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Drugging
the Undruggable: The War Against RAS Oncoproteins

(Note: companies that could be impacted by the content of this article are listed at the base of the story (desktop version). This article uses third-party references to provide a bullish, bearish and balanced point of view; sources listed in the “Balanced” section)  
The RAS pathway is one of the most frequently dysregulated pathways in cancer. Approximately 30% of tumors harbor activating RAS gene mutations. There are three main isoforms of oncogenic RAS: KRAS, HRAS and NRAS.  Among these genes, KRAS is the most frequently mutated (~90% of pancreatic cancers, ?35% of colon cancers). In comparison, NRAS and HRAS are mutated in a lesser number of cancer patients (15% of melanomas and 4% of head and neck cancer patients).
The RAS protein family consists of low molecular weight guanosine 5?-triphosphate (GTP), a building block of protein synthesis. GTP-binding proteins orchestrate a variety of cellular signaling networks, which are essential to regulate a variety of cellular functions including cell proliferation, differentiation, and cell survival. The three RAS proteins (N-RAS, H-RAS and K-RAS) oscillate between an active (GTP-bound) and an inactive (GDP-bound) state. When RAS genes are mutated (typically at codon 12, 13 or 61), RAS proteins are constitutively activated (i.e. continuously binding to GTP), which induces a pro-tumorigenic state characterized by unregulated cell proliferation and resistance to apoptosis (i.e. evading death signals). Constitutively activated RAS proteins trigger downstream signaling responsible for phenotypic traits known as hallmark of cancer including:

• aberrant cell proliferation
• resistance to apoptosis
• increase in migration, cell invasion and metastasis to different tissues
• escaping the anti-tumoral immune response

The phenotype of many cancer cells is determined by RAS-dependent aberrant signal transduction pathways involving various oncogenic proteins acting downstream of RAS (Exhibit 1).
The high mutational rate of RAS genes in cancer patients, combined with the fundamental role of RAS proteins in cancer biology, makes the RAS family of oncoproteins a primary therapeutic target. Since its discovery in 1982, both academia and industry have made significant efforts to develop an anti-cancer medicine targeting RAS. Despite these intensive efforts, there are no FDA approved anti-RAS drugs at present. For this reason, RAS is perceived as “undruggable”.
In 2013, the National Cancer Institute launched the “RAS
initiative” to expand efforts toward the discovery and development of novel medicines for the treatment of RAS-caused cancers. Since then, the initiative has focused on answering the key questions:

1. Can it be targeted directly or indirectly?
2. Which effector pathway of RAS is most crucial for cancer initiation and progression?
3. Are specific mutants or isoforms required to be specifically targeted for effective inhibition?

The enthusiasm generated by the “RAS initiative” has sparked renewed interest by the biotech and pharma industries, which has restarted their own RAS programs.
Exhibit
1. RAS signaling pathways involved in human cancer

Source:
Seminars in Cancer Biology 54 (2019) 138–148

Monday, July 8, 2019

Dyadic International (DYAI)

VTT to Continue Validation of C1 Platform in Bioproduction.

Dyadic International, Inc. is a global biotechnology company which is developing what it believes will be a potentially significant biopharmaceutical gene expression platform based on the industrially proven hyper productive engineered fungus Thermothelomyces heterothallica (formerly Myceliophthora thermophila), named C1.
The C1 microorganism, which enables the development and large scale manufacture of low cost proteins, has the potential to be further developed into a safe and efficient expression system that may help speed up the development, lower production costs and improve the performance of biologic vaccines and drugs at flexible commercial scales. Dyadic is using the C1 technology and other technologies to conduct research, development and commercial activities for the development and manufacturing of human and animal vaccines and drugs, such as virus like particles (VLPs) and antigens, monoclonal antibodies, Fab antibody fragments, Fc-Fusion proteins, biosimilars and/or biobetters, and other therapeutic proteins. Dyadic pursues research and development collaborations, licensing arrangements and other commercial opportunities with its partners and collaborators to leverage the value and benefits of these technologies in development and manufacture of biopharmaceuticals. In particular, as the aging population grows in developed and undeveloped countries, Dyadic believes the C1 technology may help bring biologic vaccines, drugs and other biologic products to market faster, in greater volumes, at lower cost, and with new properties to drug developers and manufacturers, and improve access and cost to patients and the healthcare system, but most importantly save lives.

 

Ahu Demir, Ph.D., Biotechnology Research Analyst, Noble Capital Markets, Inc.

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

• Extension of Research Agreement with VTT. Dyadic has extended its research and development contract with VTT Technical Research Centre through June 2022. VTT is a Finland-based, state owned non-profit company, which provides research and innovation services. Dyadic and VTT continuing long history of collaboration to improve production of target proteins and establish glyco-engineering for C1 platform.  
• Terms of the Agreement. The terms of the agreement include a total payment of €2.52(EUR) million throughout the 36 months of contract period. The agreement also grants… 

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CAR-T Medicines for The Treatment of Cancer, Part 2

(click here
for part one)

(Note: companies that could be impacted by the content of this article are listed at the base of the story (desktop version). This article uses third-party references to provide a bullish, bearish and balanced point of view; sources listed in the “Balanced” section)

Chimeric Antigen Receptor T cell therapy (CAR-T) is a gene therapy designed to harness the potency of antibodies and T-lymphocytes into one single medicine for the treatment of cancer. CAR-T therapy could be viewed as a “living anti-cancer drug” as the medicine itself consists of a living cell, which is genetically engineered as a pharmaceutical “chimera” to find and destroy cancer cells. The term chimera describes a monstrous being from Greek mythology composed from different animal parts. It appears in literature as a creature with two heads: a lion’s and a goat’s (see Figure 1 below). Like the creature from Greek mythology, a CAR-T medicine also has two heads: antibody binding domain and T-cell receptor (TCR) signaling domain.

Figure 1: According to Greek mythology, a Chimera was a hybrid with
parts from different animals. It consisted of a lion with a goat’s head and a
tail ending in snakes’ heads. In the Homer’s Iliad, a chimera is described as a
“fearsome beast snorting out the breath of terrible flame of bright fire”.

Source
– Chimera, Greek Mythology, www.mythortruth.com

In
science, the term chimera is often used to describe hybrids from different
species, such as a virus with DNA sequences from different species, or a CAR-T
drug construct consisting of an antibody fused to a T lymphocyte, combining the
medical potency of an anti-cancer antibody with the cancer killing properties
of a T lymphocyte. (read Part 1 of the CAR-T
article series here)

Wednesday, June 19, 2019

TherapeuticsMD (TXMD)

What Investors are Missing

TherapeuticsMD Inc is a major drug manufacturing with a focus on creating and commercializing products targeted exclusively for women. The company intends to commercialize advanced hormone therapy pharmaceutical products. 

Ahu Demir, Ph.D., Biotechnology Research Analyst, Noble Capital Markets, Inc.

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

• The stock slides. TXMD shares are down 15% since the company held its analyst day on June 10, 2019. We believe that the shares overreacted to management’s weak revenue outlook which anticipates 87% revenue growth for the full year 2019 (21% below consensus revenue expectations). We estimate that revenues will show an accelerated growth in subsequent years, up 180% in 2020, up 346% in 2021 and up 108% in 2022.
• The bigger picture. We believe that there are encouraging revenue attributes; 1) the company’s product, Imvexxy, had solid upward Q1 revenue trajectory, surpassing…

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Tuesday, June 11, 2019

electroCore (ECOR)

Choppy Waters for electroCore

electrocore Inc is a commercial-stage bioelectronic medicine company with a platform for non-invasive vagus nerve stimulation therapy initially focused on neurology and rheumatology. Its product gammaCore is FDA-cleared for the acute treatment of pain associated with migraine and episodic cluster headache in adults.

 

Ahu Demir, Ph.D., Biotechnology Research Analyst, Noble Capital Markets, Inc.

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

• CEO Frank Amato Departs. Yesterday, electroCore announced another departure from the leadership team since the annual shareholder meeting held on June 7, 2019. Frank R. Amato is leaving the company after serving as a Chief Executive Officer since 2016. He will continue to serve as the CEO and board member until a new CEO is recruited. This position is expected to be filled before September 30, 2019.
• Restructuring Continues.We expect the company to pursue additional steps to reshape the leadership team following two departures within the past week. Besides Frank’s departure… 

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NOTE: investment decisions should not be based upon the content of
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CAR-T and the Possibility of Cancer Treatment, Part 1

style=”margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: Calibri, sans-serif;”>click her for part two of this article series

(Note: companies that could be impacted by the content of this article are listed at the base of the story (desktop version). This article uses third-party references to provide a bullish, bearish and balanced point of view; sources listed in the “Balanced” section)

Chimeric Antigen
Receptor T cell therapy (CAR-T) is a gene therapy designed to harness the
potency of antibodies and T-lymphocytes into one single medicine for the
treatment of cancer. CAR-T therapy could be viewed as a “living anti-cancer
drug” as the medicine itself consists of a living cell, which is genetically
engineered to find and destroy cancer cells. Dr. Carl H. June pioneered this
technology at the University of Pennsylvania, where the first tests were
conducted in cancer patients in 2010. Seven years later, the U.S. Food &
Drug Administration (FDA) approved this novel gene therapy for the treatment of
patients suffering from “B-cell precursor acute lymphoblastic leukemia” (ALL),
a type of blood cancer known to be the most common malignant growth in
children.

Thus far, anti-cancer
antibodies have been one of the most successful drug classes for the treatment
of cancer patients. Antibody drugs such as Roche’s Avastin, Herceptin and Rituxan have prolonged survival of many
cancer patients. Another class of medicines, known as T-infiltrating
lymphocytes (TILs), has been shown to be effective as an anti-cancer treatment.
Given the relative success of both therapeutic strategies, the question is, how
do you combine both treatments into one potent anti-cancer drug?

CAR-T represents
the solution to this riddle. CAR-T consists of two main components: 1) the
tumor associated antigen (TAA) domain of an anti-cancer antibody (scFV) linked through
a spacer/transmembrane region to 2) the cytoplasmic domain of the receptor of a
cancer-killing T lymphocyte. The new anti-cancer drug, CAR-T, is a genetically
engineered T-lymphocyte expressing a chimeric T cell receptor on its surface
(Figure 1). This chimera consists of the binding domain of the antibody
(external domain protruding from the cell surface), fused to the signaling portion
CD3 of the T cell receptor (internal domain facing the cellular cytoplasm).

Figure 1 – Structure of a CAR-T construct. The left panel depicts a
CAR-T medicine (first generation), whereas the right panel depicts the natural
T cell receptor, TCR. In the CAR-T construct (left panel), the binding domain
(light blue/purple) of an anti-cancer antibody (scFV) replaces the alpha/beta
chain portion (green/red) of the natural TCR (right panel). The transmembrane
and cytoplasmic components of CAR-T and TCR, including CD3 domain, are depicted
in blue.

 

Source – Oncotarget 2015,
8(52)90521-90531 ?

To generate a
CAR-T drug, five main steps are required (Figure 2):

1. blood from the patient is extracted
2. T-lymphocytes are purified from extracted
   blood, and subsequently genetically modified to express the CAR chimeric
   receptor
3. CAR-T cells are grown in vitro (ex vivo)
4. Once CAR-T cells are grown to reach a
   therapeutic dose, they are injected back into the patient
5. Injected CAR-T cells are engineered to find
   and kill cancer cells

Source – The University of Texas
Southwestern Medical Center

Wednesday June 5, 2019

electroCore (ECOR)

Continuing Execution of the Redeployment Plan

Electrocore Inc is a commercial-stage bioelectronic medicine company with a platform for non-invasive vagus nerve stimulation therapy initially focused on neurology and rheumatology. Its product gammaCore is FDA-cleared for the acute treatment of pain associated with migraine and episodic cluster headache in adults.  

Ahu Demir, Ph.D., Biotechnology Research Analyst, Noble Capital Markets, Inc.

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

Founder and Chief Science and Strategy Officer departs. electroCore announced another event as part of the redeployment plan that emerged on May 29. Founder Joseph P. Enrico, who served as the Company’s Chief Science and Strategy Officer,  agreed to leave the company, effective as of June 8, 2019. He co-founded the company in 2005 and served in multiple roles including Chief Executive Officer (CEO) prior taking his current role in 2016. He remains as a Board Director and holds 2.2% equity stake in the company.

Chief Medical Officer to take over the strategy role. Management stated plans to continue with the current leadership team. Tony Fiorino, M.D. Ph.D. will continue to serve as Chief…

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Friday, May 31, 2019

electroCore (ECOR)

Can the Reduced Cash Burn Calm Ragged Nerves?

Electrocore Inc is a commercial-stage bioelectronic medicine company with a platform for non-invasive vagus nerve stimulation therapy initially focused on neurology and rheumatology. Its product gammaCore is FDA-cleared for the acute treatment of pain associated with migraine and episodic cluster headache in adults.  

Ahu Demir, Ph.D., Biotechnology Research Analyst, Noble Capital Markets, Inc.

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

• Concern around the high cash burn is lowered. electroCore implemented a cost reduction and deployment plan reducing the cash burn to $2.3 million from $4 million per month, effective by June 2019. We view extension of the cash runaway as a positive road map for the company, but we believe the stock will remain under pressure until the company shows a solid revenue ramp-up.
• Basis of the cost reduction plan. The cost reduction was endowed by i) reducing work force to 55 positions from 91 – eliminating sales, medical affairs personnel, ii) abolishing cash compensation of board servicing by independent directors, iii) voluntary acceptance of stock compensation in lieu of cash compensation by Chief Executive Officer Francis Amato and iv) postponing current clinical operations – to be determined following the company’s board meeting on June.

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NOTE: investment decisions should not be based upon the content of
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