On December 3, 2018 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported the presentation of preclinical data from the Company’s Menin-Mixed Lineage Leukemia (MLL) inhibitor program at the 60thAmerican Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California (Press release, Syndax, DEC 3, 2018, View Source [SID1234531831]).

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"Acute leukemias characterized by MLL-rearrangements (MLL-r) and nucleophosmin (NPM1) mutations represent areas of high unmet medical need, with 5-year survival rates falling below 50%," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "Data presented on VTP-50469, a Syndax Menin-MLL inhibitor, provides further support for developing this class of molecules for specific, genetically-defined acute leukemias. The robustness and consistency of the accumulated preclinical data seen with our Menin-MLL inhibitors provide support for an anticipated IND filing on our lead compound, SNDX-5613, in the second quarter of 2019."

In an oral presentation at ASH (Free ASH Whitepaper), Hannah Uckelmann, Ph.D., Dana-Farber Cancer Institute, presented new preclinical data demonstrating that NPM1 mutant progenitor cells can act as drivers of leukemic transformation, and that VTP-50469 can block their pathological capacity by disrupting the menin-MLL interaction. In addition, data generated using a mouse PDX model of NPM1 mutant acute myeloid leukemia (AML) demonstrated that single agent treatment with VTP-50469 eradicated pre-leukemic NPM1 mutant cells and prevented leukemia development, resulting in a marked survival benefit. These data lend further support to the potential therapeutic utility of menin inhibitors in the setting of NPM1 mutant AML.

Furthermore, during a Scientific Spotlight Session at ASH (Free ASH Whitepaper), Scott Armstrong, M.D., Ph.D., Dana-Farber Cancer Institute, provided an overview of the multiple complexes that influence gene expression in MLL-r leukemias and NPM1 AML. Additional preclinical data generated in his laboratory further substantiate that inhibition of the Menin-MLL interaction can decrease leukemic burden and prolong survival in mouse PDX models of both MLL-r and NPM1 mutant leukemias. These data build on prior encouraging preclinical results presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April, and further underscore the potential therapeutic utility of menin inhibitors as modulators of critical epigenetic mechanisms in acute human leukemias, including subsets of both acute lymphoblastic leukemia (ALL) and AML.

Oral Presentation:

Title: MLL-Menin Inhibition Reverses Pre-Leukemic Progenitor Self-Renewal Induced By NPM1 Mutations and Prevents AML Development
Presenter: Hannah Uckelmann, Ph.D., Research Fellow at the Dana-Farber Cancer Institute
Publication Number: 546

Scientific Spotlight Session:

Title: Targeting Chromatin Complexes in MLL Rearranged Leukemia
Presenter: Scott Armstrong, M.D., Ph.D., Chairman of the Department of Pediatric Oncology at the Dana-Farber Cancer Institute, Associate Chief of the Division Hematology/Oncology at Boston Children’s Hospital, and the David G. Nathan Professor of Pediatrics at Harvard Medical School

Both presentations are available in the Publications section of the Company’s website, www.syndax.com.

About MLL Rearranged Leukemias

Rearrangements of the MLL gene give rise to an acute leukemia, MLL-r. MLL-r occurs in ~80% of infant acute leukemias and up to 10% of adult acute leukemias. It is associated with a poor prognosis, with less than 50% of infants with MLL-r surviving past 5 years. MLL rearrangements produce fusion proteins that require interaction with a protein called Menin in order to drive leukemic cancer growth. Disruption of the Menin-MLL-r interaction has been shown to halt the growth of MLL-r leukemic cells. MLL-r leukemias are routinely diagnosed through currently available cytogenetic screening techniques in leukemic cells, but there are currently no approved therapies indicated for MLL-r leukemias.

About NPM1c Acute Myeloid Leukemia

NPM1c represents another discrete form of acute myeloid leukemia (AML) distinguished by point mutations in the NPM1 gene that drives the leukemic phenotype. NPM1c is the most common type of cytogenetically normal AML and represents ~30% of all diagnosed AML. This subtype of AML has a poor prognosis, with a 5-year overall survival rate of ~50%. Similar to MLL-r leukemias, NPM1c AML is highly dependent on the expression of specific developmental genes, shown to be negatively impacted by inhibitors of the menin-MLL1 interaction. NPM1c AML is routinely diagnosed through currently available screening techniques in leukemic cells, but there are currently no approved therapies indicated for NPM1c AML.

On December 3, 2018 TRACON Pharmaceuticals (Nasdaq: TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, and I-Mab Biopharma ("I-Mab"), a China-based clinical stage biopharmaceutical company exclusively focused on the development of innovative biologics in immuno-oncology and autoimmune diseases, will host a conference call and webcast on Wednesday, December 5, 2018, to discuss the recently announced series of strategic collaborative partnerships for developing multiple immuno-oncology programs (Press release, Tracon Pharmaceuticals, DEC 3, 2018, http://ir.traconpharma.com/news-releases/news-release-details/tracon-pharmaceuticals-and-i-mab-biopharma-host-conference-call [SID1234531830]).

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Wednesday, December 5th @ 4:30pm Eastern Time
US Investors: 877-407-9039
International: 201-689-8470
Passcode: 13685586
Webcast: View Source

Replays, Available through December 19th:
Domestic: 844-512-2921
International: 412-317-6671
Replay PIN: 13685586
About TRACON
TRACON develops targeted therapies for cancer and ophthalmic diseases. The Company’s clinical-stage pipeline includes: TRC105, an endoglin antibody that is being developed for the treatment of multiple cancers; DE-122, the ophthalmic formulation of TRC105 that is being developed in wet AMD by corporate partner Santen Pharmaceutical Company Ltd.; TRC102, a small molecule being developed for the treatment of lung cancer and solid tumors; and TRC253, a small molecule being developed for the treatment of prostate cancer. To learn more about TRACON and its product candidates, visit TRACON’s website at www.traconpharma.com.

About I-Mab
I-Mab is a dynamic and fast-growing global company exclusively focused on developing first-in-class and best-in-class biologics in the areas of immuno-oncology and autoimmune diseases through internal R&D capabilities and global partnerships. I-Mab’s pipeline is driven by the company’s development strategy to address unmet needs in China and to bring innovative assets to the world. The company is prepared to submit additional INDs in order to initiate clinical trials in China and the U.S., including multiple Phase II and Phase III studies. I-Mab is on a fast track towards becoming an end-to-end fully integrated biopharma company. The company has been well-recognized by capital markets with the recent $220 million Series C financing representing one of the largest amounts ever raised by an innovative biotech company in China. www.i-mabbiopharma.com

On December 3, 2018 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or "the Company"), reported that updated data from its Phase 2 trial of Actimab-A was highlighted in a poster presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Actinium Pharmaceuticals, DEC 3, 2018, View Source [SID1234531829]). The Actimab-A Phase 2 trial studied the ARC or Antibody Radiation Conjugate Actinium-225 – lintuzumab, which delivers potent alpha particle radiation to CD33 expressing cells, in patients with untreated AML over the age of 60 that are unfit for induction chemotherapy. Patients received fractionated doses of Ac-225 – lintuzumab on days 1 and day 8. The poster presented at ASH (Free ASH Whitepaper) highlighted data from a second cohort of 27 patients that received 1.5 µCi/kg/fraction.

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Dr. Mark Berger, Actinium’s Chief Medical Officer said, "In this difficult to treat patient population, we are pleased to have observed this level of single-agent activity from Actimab-A with the benefit of minimal extramedullary toxicities. These results strongly support continued development and we have prioritized highly attractive areas that can leverage the strengths of our ARC approach. A major initiative is our Actimab-MDS trial where we have a clear pathway to a pivotal trial established with the FDA for high-risk patients with myelodysplastic syndromes. Another exciting opportunity is via combination trials with agents like venetoclax in the relapsed, refractory AML setting where the apparent synergy of mechanisms can translate to a therapeutic advantage. In addition, we are pursuing other highly-differentiated opportunities for Actimab-A as a single-agent in patients with high unmet needs where the extremely high-potency of an ARC can be used safely at low doses. An example is our novel trial in AML patients with minimal residual disease post-remission."

Overall response rate in this dosing cohort was 22% (6/27) with 3 CRps and 3 CRis. Among responding patients, 2 had adverse cytogenetics and 1 had previous MDS. This data is in addition to previously reported data from 13 patients that were treated at an original dose cohort of 2.0 µCi/kg/fraction where a 69% overall response rate was reported. The dose was lowered to 1.5 µCi/kg/fraction due to myelosuppression lasting longer than 6 weeks, which resulted in a reduction in the incidence of prolonged thrombocytopenia from 46% to 30%.

The median age of patients in this cohort of the Phase 2 trial was 75 (60 -87) with 81% of patients having ECOG performance status of 1 (13/27) or 2 (9/27). Although patients had untreated acute myeloid leukemia (AML), 52% (14/27) of patients had prior hematologic disease with 79% (11/14) having myelodysplastic syndrome (MDS), 14% (2/14) having chromic myelomonocytic leukemia (CMML) and 7% (1/14) having myelofibrosis. A majority of patients had unfavorable cytogenetics with 56% (15/27) having intermediate-risk and 26% (7/27) having high-risk cytogenetics. In addition, patients were evaluated for CD33 splicing polymorphism and responses occurred irrespective of cytogenetic risk category or splicing genotype.

Actinium also highlighted that preliminary preclinical data from its Iomab-ACT program was highlighted in the ASH (Free ASH Whitepaper) supplemental edition of blood. Actinium’s preclinical studies showed a considerable reduction in both lymphocyte and myeloid cell counts, inclusive of immune suppressive regulatory T cells and myeloid derived suppressor cells. Further, the cytoreduction by CD45-RIT was shown to induce the expression of immune homeostatic cytokines including IL-15.The abstract can be accessed he View Source

Sandesh Seth, Actinium’s Chairman and CEO said, "Given the recent and increasing competition in AML, we believe the future development pathways selected by our team strategically differentiate Actinium’s CD33 program in a manner that can maximize value creation. We have done this by focusing on an area with limited or no competition via Actimab-MDS in targeted conditioning. We have also leveraged our AWE or Antibody Radiation Conjugate technology platform to add a different modality, namely targeted radiation, to other areas of unmet or underserved needs as evidenced by our Actimab-A plus Venetoclax combinations and Actimab-A MRD trials. With our lead asset, Iomab-B progressing well in its pivotal trial, the near-pivotal Actimab-MDS program and the Iomab-ACT program for lymphodepletion prior to CAR-T, our multi-asset pipeline will enable our company to build a franchise opportunity in targeted conditioning which is almost singular in the industry."

On December 3, 2018 Sesen Bio, Inc. (Nasdaq: SESN), a late-stage clinical company developing targeted fusion protein therapeutics for the treatment of people with cancer, reported the appointment of Dennis Kim, M.D., MPH, as chief medical officer (Press release, Sesen Bio, DEC 3, 2018, View Source [SID1234531828]). In this role, Dr. Kim will oversee the continued Phase 3 development of Vicinium, Sesen Bio’s lead targeted fusion protein, for patients with high-grade non-muscle invasive bladder cancer (NMIBC), as well as preparations for a marketing authorization submission and pre-commercial activities.

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"We are thrilled to welcome Dennis to the Sesen Bio team and look forward to leveraging his deep drug development experience, particularly as we approach both six and 12-month data readouts from our VISTA Trial of Vicinium," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. "Dennis has an extensive track record of leading product candidates through development to approval and commercial launch. As the Vicinium program advances, his leadership will be instrumental in helping us bring this novel treatment to patients in need and achieving our mission of saving and renewing the lives of people with cancer."

Dr. Kim brings significant drug development and commercialization experience to Sesen Bio’s leadership team. He has played key roles in both the approval and commercial launch of more than 10 products in oncology and immunology. Prior to joining Sesen Bio, Dr. Kim held senior and leadership roles at Ipsen, Spectrum, Novartis, Biogen Idec, and Amgen. Previously, Dr. Kim was an Epidemic Intelligence Service Officer at the Centers for Disease Control and Prevention where he played active roles in environmental and infectious disease studies. Dr. Kim earned his bachelor’s degree in chemistry and biology from Harvard, his M.D. from Stanford University and his MPH from the University of California, Los Angeles.

"I am highly encouraged by the data generated to date with Vicinium in high-grade non-muscle invasive bladder cancer, and believe this therapy has the potential to change the way we treat bladder cancer," said Dr. Kim. "I am excited to work with the Sesen Bio team and board of directors to help propel Vicinium towards a potential approval so that we can help the many patients, and their families and physicians, who need a new and effective treatment option for this devastating cancer."

In connection with the appointment of Dr. Kim, Sesen Bio entered into an employment agreement with Dr. Kim that, among other things, provides for the grant of a non-statutory stock option outside of Sesen Bio’s 2014 Stock Incentive Plan as an inducement material to Dr. Kim’s entering into employment with Sesen Bio in accordance with Nasdaq Stock Market Listing Rule 5635(c)(4). The stock option to purchase 425,000 shares of the company’s common stock is being granted effective as of December 3, 2018. The stock option grant was approved by the independent compensation committee of the board of directors in accordance with Nasdaq Stock Market Listing Rule 5635(c)(4). This stock option will have an exercise price per share equal to the closing price per share of Sesen Bio’s common stock on The Nasdaq Global Market on December 3, 2018. The stock option will have a ten-year term and will vest over a four-year period, with 25 percent of the shares underlying the stock option award vesting on the first anniversary of the date of grant and an additional 6.25 percent of the shares underlying the stock option vesting at the end of each successive three-month period following the one-year anniversary of the date of grant of the stock options, subject to Dr. Kim’s continued service with the company through the applicable vesting dates.

On December 3, 2018 Geron Corporation (Nasdaq: GERN) reported that updated results from Part 1 of IMerge, the Phase 2 portion of a Phase 2/3 clinical trial of imetelstat in lower risk myelodysplastic syndromes (MDS), were presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California on December 2, 2018 (Press release, Geron, DEC 3, 2018, View Source [SID1234531827]). The oral presentation was made by David Steensma, M.D., Institute Physician at the Dana-Farber Cancer Institute and Associate Professor at Harvard Medical School, and an IMerge clinical investigator. Geron believes these results support initiating the Phase 3 portion of IMerge to address an unmet medical need for patients for whom erythropoiesis stimulating agents (ESAs) are not effective and for whom currently available therapies show only modest efficacy.

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"The results from the Phase 2 portion of IMerge presented at ASH (Free ASH Whitepaper) highlight imetelstat’s broad clinical activity, especially in difficult-to-treat patients, as indicated by the high baseline transfusion burden of the patients enrolled in IMerge. As such, we believe imetelstat could offer a much-needed alternative treatment in lower risk MDS," said John A. Scarlett, M.D., Geron’s President and Chief Executive Officer. "We remain committed to developing imetelstat and continue to plan the initiation of the Phase 3 portion of IMerge by mid-year 2019."

IMerge Phase 2/3 Clinical Trial Design

IMerge is a two-part clinical trial evaluating imetelstat in transfusion dependent patients with Low or Intermediate-1 risk MDS who have relapsed after or are refractory to prior treatment with an ESA. The first part of the trial was originally designed as a Phase 2, open-label, single-arm trial to assess the efficacy and safety of imetelstat. The second part of the trial is planned as a Phase 3 double-blind, randomized, placebo-controlled trial in approximately 170 patients. To be considered for enrollment into IMerge, patients had to be transfusion dependent, requiring ≥4 units of red blood cells (RBC) over 8 weeks prior to entry into the trial. The primary efficacy endpoint of the trial is the rate of RBC transfusion-independence (RBC TI) lasting at least 8 weeks, defined as the proportion of patients without any RBC transfusion during any consecutive 8 weeks since entry into the trial. Key secondary endpoints are the rate of ≥24-week RBC TI and the rate of hematologic improvement-erythroid (HI-E), defined as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least 8 weeks or a reduction of at least 4 units of RBC transfusions over 8 weeks compared with the prior RBC transfusion burden.

Among the first 32 patients enrolled in the Phase 2 portion of IMerge, an initial cohort of 13 patients, who were non-del(5q) and naïve to HMA and lenalidomide treatment, showed an increased RBC TI rate and durability compared to the overall trial population. Thus, earlier this year, an additional expansion cohort of 25 patients were enrolled who were non-del(5q) and naïve to HMA and lenalidomide treatment in order to increase the experience and confirm the benefit-risk profile of this target patient population.

Clinical Data Presentation

Title: Imetelstat Treatment Leads to Durable Transfusion Independence (TI) in RBC Transfusion-Dependent (TD), Non-Del(5q) Lower Risk MDS Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Who Are Lenalidomide and HMA Naïve (Abstract #463)

The oral presentation described combined data with a data cut-off date of October 26, 2018 for the target patient population (n=38) in the Phase 2 portion of IMerge, which includes 13 patients from the initial cohort and 25 patients from the expansion cohort. The initial cohort had a median follow up time of 29 months, and the expansion cohort had a median follow up of almost nine months. As of the data cut-off date, median duration of RBC TI had not been reached for the target patient population. Geron expects further data from the Phase 2 portion of IMerge for the target patient population reflecting longer follow up to be available in 2019 and anticipates submitting such data for presentation at a future medical conference.

Efficacy Highlights for Target Patient Population (n=38):

37% (14/38) of patients achieved ≥8-week RBC TI
26% (10/38) of patients achieved ≥24-week RBC TI
Rate of transfusion reduction (HI-E) was 71% (27/38)
Mean relative reduction of RBC transfusion burden from baseline was 68%
Broad clinical activity observed
• Similar 8-week RBC TI was observed in patients with baseline serum erythropoietin (sEPO) levels less than or greater than 500mU/mL
• 8-week RBC TI consistent across ring-sideroblast (RS) patient subtypes, RS+ and RS-
Reductions in mutation burden and presence of RS noted among responding patients, suggesting potential disease modifying activity
Safety Summary for Target Patient Population (n=38):

Cytopenias, particularly neutropenia and thrombocytopenia, were the most frequently reported adverse events which were predictable, manageable and reversible
The slides from the oral presentation at ASH (Free ASH Whitepaper) are available on Geron’s website at www.geron.com/r-d/publications.

Phase 3 Development Plan for Lower Risk MDS

Based on the combined data from the initial and expansion cohorts for the target patient population in the Phase 2 portion of IMerge, Geron plans to initiate the Phase 3 portion of IMerge after the sponsorship of the ongoing imetelstat clinical trials has been transferred back to Geron. Geron anticipates patient screening and enrollment for the Phase 3 portion of IMerge to begin by mid-year of 2019.

Analyst and Investor Event

On December 10, 2018, Geron will host a webcasted event for analysts and investors. At the event, Dr. Azra Raza, a clinical investigator for IMerge, will reprise the oral presentation made at the ASH (Free ASH Whitepaper) Annual Meeting, as well as describe the unmet medical need in lower risk MDS. A live audio webcast of the event will be available on Geron’s website, www.geron.com/investors/events. If you are unable to listen to the live presentation, an archived webcast of the event will be available on the Company’s website for 30 days.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat include a Phase 2/3 trial called IMerge in lower risk myelodysplastic syndromes (MDS) and a Phase 2 trial called IMbark in Intermediate-2 to High-risk myelofibrosis. Imetelstat received Fast Track designation from the United States Food and Drug Administration for the treatment of patients with transfusion-dependent anemia due to lower risk MDS who are non-del(5q) and refractory or resistant to an erythroid stimulating agent