In December of this year, the annual American Society of Hematology (Ash) meeting will take place for the 59th time. Ash is the premier event in malignant and non-malignant hematology where a lot of publicly traded companies give clinical trial updates which are often times high value binary-type events. These meetings not only provide investors with updates on companies they have invested in, but also offer biotech catalyst traders solid opportunity to take advantage of what is called ‘the biotech run-up catalyst trade.’
Additionally, we also see many developmental companies engage in significant partnerships right before, or immediately after this annual meeting. Below, we highlight 4 companies we have done extensive research on which we feel could see substantially strong upside movement before and after The Ash meeting.
Note: Abstracts for Ash poster presentations become un-embargoed November 1st.
Glycomimetics (GLYC) is a name we have more extensively covered in an articlefrom mid-May of this year. The company is focused on the development of glycomimetic drug compounds to interact with cell surface adhesion and trafficking. At Ash, we will be watching for an update to the positive developments we have seen so far from the company’s wholly owned GMI-1271. For those who aren’t familiar, GMI-1271 is a highly selective E-selectin antagonist which has demonstrated activity in both front-line and relapsed/refractory (r/r) Acute Myeloid Leukemia (AML). The compound is designed to be cycled before, during, and after chemo and in r/r disease has shown a 41% Complete Remission rate (CR+CRi) comparing favorably to 28% with Mitoxantrone, Etoposide, & Cytarabine (MEC) alone. Perhaps even more impressive was the reduction in toxicity, notably for oral mucositis/stomatitis where the demonstrated severe adverse event (sAE) rate dropped to 2% vs 25% historically. Since E-selectin is often expressed on endothelial cells (which include tissue lining the oral cavity and stomach), this offers a level of mechanistic validation for GMI-1271.
The data so far has provided the basis for the FDA to grant breakthrough designation (BTD) in the r/r setting which is more broadly based on reversing toxic side-effects (Mucositis) from Chemotherapy. Investors will be looking for further follow up of the phase 2 arm of the trial which completed enrollment in May, particularly durability and possible correlations between survival benefit and E-selectin expression levels. When examining the pending data, one should keep in mind that E-selectin is often a negative prognostic indicator for disease.
This is because the expression of E-selectin allows tumor cells to escape and bind to the bone marrow, avoiding chemotherapy. As such, this marker is more often expressed in relapsed patients. Validation in AML should also provide an even more positive read through for the company’s work in Multiple Myeloma, where the company has been uncovering how E-selectin functions as a resistance mechanism to standard of care therapy. A positive correlation to response in addition to the mucositis safety benefit should lead to a clear registrational path in r/r AML – the company intends to provide an update for this in the 4th quarter.
Affimed (AFMD) has gone through a bit of a dry-spell of data leaving investors mostly uninterested in the name. However, one shouldn’t grow too complacent with this company as it will be providing efficacy data from the first 12 patients enrolled in the AFM13+Keytruda combination study in Hodgkin’s Lymphoma (NYSE:HL). AFM-13 is a bispecific antibody targeting the CD30 receptor and engaging NK cells as the effector through the CD16A receptor (more about the company from our original piece here).
In the AFM13+Keytruda trial, 6 patients so far have been enrolled at the highest dose cohort where maximum tolerated dose (NYSE:MTD) has not been reached. While this is a small data set, the historical CR rates of PD-1 agents such as Keytruda alone in this setting range in the low teens. A signal of at least two complete responders at the high dose cohort would be viewed as highly constructive. Also, of note the company will be providing information on its bio-markering work with Columbia University to provide further insights on mechanistic validity.
In the company’s recent calls, CEO Adi Hoess has begun to introduce this idea of CAR-NK synapses being generated inside the patient. After treatment with an Affimed CD16a engager, it has been observed that the drug’s efficacy may be driven by the bound drug and not plasma levels. This is a fundamentally different PK/PD profile than bispecific constructs to date – further color on this unique property may provide a catalyst for the company to valuate much higher.
Miragen Therapeutics (MGEN) is a name we have been looking closer at lately as a potentially novel upstream approach to the treatment of a variety of diseases. Miragen Therapeutics is focused on developing a unique subset of RNA biology known as micro RNA or miRNA. In short, miRNA interact with whole networks of protein transcripts and could be the driver of shifts in cell polarity, functioning as small but powerful keys to genome regulation. At Ash, the company guided for an update for its lead product MRG-106, an inhibitor of mir-155.
Mir-155 has been implicated in the regulation T- and B-cell differentiation, proliferation, and epigenetic state. It is currently being evaluated in a common subtype of cutaneous t-cell lymphoma (CTCL) known as mycosis fungoides (MF). MF functions as a proof of concept tumor type due to easy accessibility to the neoplasm for serial bio-markering. CTCL is also a rather significant unmet need area given that few currently FDA approved single agents can achieve meaningful potency. Combination approaches such as gemcitabine and bexarotene demonstrate a PR rate in the 30% range, but there is a significant toxicity draw-back to the combination approach.
To date, MRG-106 has demonstrated a 50% PR rate as measured by an improvement in the modified Severity-Weighted Assessment Tool (mSWAT) score of at least 50%. In CTCL, mSWAT represents the total surface area of the skin impacted by this disease. More notably, toxicity rates after multiple administrations of MRG-106 ranging from 300-900mg either subcutaneously, or through a 2-hour IV have been promising. There have been no observed severe adverse events (defined as grade 3+) so far in the current trial – quite encouraging given the struggles that other miRNA companies such as Regulus (RGLS) or Mirna Therapeutics (MIRN) have faced with their approaches.
Following a June meeting with the FDA, the company has decided to tack on additional arms for adult t-cell leukemia/lymphoma (ATLL), diffuse large b-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL). Validation in this initial foothold market of CTCL may provide a read through to these other high-need indications.
Syros Pharmaceuticals Inc (SYRS) like Miragen, has shown interest in regulation of expression in genes as a key driver of disease. The company has developed a unique discovery platform which allows it to screen through a plethora of patient samples of both healthy and diseased tissue. This platform looks for key similarities and differences in the regulatory region of the genome, honing in on ‘super-enhancers.’
These super-enhancers function as genetic dimmer switches controlling the transcription of the genome to RNA, whereas miRNA control the translation of these RNA to proteins. Through comparing super-enhancer regions between diseased and healthy samples, new targets of genetic regulation can be defined.
The company’s lead asset is SY-1425, a Retinoic acid receptor alpha (RAR-α) agonist. SY-1425 was originally marketed under the generic name tamibarotene in Japan for the treatment of a subset of AML known as Acute Promyelocytic Leukemia (APL) which is fundamentally characterized by a translocation in the RAR-α gene.
As a single agent in this setting, the safety and tolerability profile has already been well established. The compound has shown a respectable efficacy of 58% CR rate in APL. Syros has found that a larger number (about 33-40%) of MDS and AML patients who weren’t diagnosed as APL, still expressed biomarkers for the RAR-α pathway activation. As such, the company in-licensed the compound in the U.S. and Europe and are filing for proprietary patents in these settings, providing coverage for 2036+. The company will provide initial clinical data for SY-1425 as a single agent at Ash. Recent biomarker work published indicates that SY-1425 may also sensitize patients to CD38 by inducing maturation, providing further opportunity for the company in expanded settings.
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