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Gotham Therapeutics Launches with $54 Million Series A

On October 10, 2018 Gotham Therapeutics, a biotechnology company developing a novel drug class targeting RNA-modifying proteins, reported with a $54 million Series A financing co-led by founding investor Versant Ventures, Forbion and S.R. One (Press release, Gotham Therapeutics, OCT 10, 2018, View Source [SID1234550889]). The syndicate also included Celgene Corporation and Alexandria Venture Investments. Gotham is part of New York’s rapidly growing biopharma community with a subsidiary at one of Europe’s leading life science clusters near Munich, Germany.

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Versant created and seeded Gotham based upon the seminal discoveries of co-founder Samie Jaffrey, M.D. Ph.D., a pioneer in an exciting new field within RNA metabolism called epitranscriptomics. Dr. Jaffrey is a professor of pharmacology at Weill Cornell Medicine and a member of the Scientific Advisory Board for Gotham Therapeutics. His work has shed light on the role of post-transcriptional mRNA modifications in health and disease. These modifications and their biological effects are driven by protein complexes commonly described and categorized as writers, erasers and readers of the epitranscriptomic code.

With its seed funding, Gotham built a platform to assess the impact of RNA-modifying proteins on disease biology and developed small molecules against priority targets. The Series A proceeds will allow Gotham to establish clinical proof of concept and to invest broadly in a pipeline of preclinical candidates that have potential to treat diseases intractable to classical approaches.

"As we pursue several important targets, the information we glean will help us further validate and build our platform for increasingly broad applications. Our goal is to become the leader in drugging key proteins that modulate mRNA functionality, thereby impacting disease onset and progression," said Lee Babiss, Ph.D., CEO of Gotham.

"While academic research and the pharmaceutical industry focused initially on modifications of DNA, a growing body of evidence indicates that mRNA modifications help determine to which degree genes are translated into proteins. RNA modifications and their associated protein complexes therefore represent an untapped frontier that could yield new therapeutic approaches," added Dr. Jaffrey.

Gotham has assembled an experienced founding team led by Dr. Babiss, former President of Pharma Research at Roche. Dr. Babiss is an early adopter of RNA drug discovery approaches who has a track record of translating discoveries into therapeutic candidates. He also has served as CSO of PPD, and as Head of Human Genetics and Personalized Healthcare at Glaxo Wellcome.

"After following the developments in the RNA drug discovery field for a number of years, we felt this was the right time to build a company that could capitalize on translating the scientific discoveries into a whole new class of drug candidates," said Carlo Rizzuto, Ph.D., Partner at Versant. "With our initial investment, the Gotham team constructed a platform able to validate critical links between specific types of RNA modifications and disease biology. We look forward to advancing a number of drug candidates with this new round of financing."

"We are excited to invest in Gotham, one of the pioneers in the fast-emerging field of RNA metabolism, which could create a paradigm shift in both cancer therapy and other major diseases," commented Holger Reithinger, Ph.D., General Partner at Forbion. "Gotham represents the first investment by our recently announced Forbion IV fund. Our new fund aims to help build leading companies around exciting new science, proven teams or in-licensed assets."

Dr. Reithinger will join Dr. Babiss, Dr. Rizzuto and Jill Carroll, Principal, SR One, on Gotham’s Board of Directors. Jorge DiMartino M.D., Ph.D., Vice President, Translational Development Oncology at Celgene and Head of Celgene’s Epigenetics Thematic Center of Excellence, has joined the board in an observer role.

Sermonix Launches Phase 2 Trial to Evaluate Investigational Oral Lasofoxifene as a Targeted Precision Treatment for Women With ESR1 Mutations in Metastatic Breast Cancer

On October 10, 2018 Sermonix Pharmaceuticals LLC, a privately held biopharmaceutical company focused on the development and commercialization of female-specific oncology products, reported the launch of a Phase 2 trial for the treatment of metastatic breast cancer (Press release, Sermonix Pharmaceuticals, OCT 10, 2018, View Source [SID1234532258]). The program is an open-label, randomized, multi-center study evaluating the activity of its lead investigational drug, oral lasofoxifene, versus intramuscular fulvestrant for the treatment of postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer with an ESR1 mutation.

"Clinical data have shown a significant reduction in the incidence of ER+ breast cancer in postmenopausal women with osteoporosis who were treated with lasofoxifene," said Paul Plourde, MD, Sermonix vice president of clinical development. "Additional non-clinical and clinical study results provide further impetus for undertaking a Phase 2 trial in a targeted way that compares lasofoxifene to fulvestrant, a current, widely used injectable medication for advanced metastatic breast cancer."

Linical Accelovance Group, a mid-size global contract research organization, will serve as Sermonix’s research partner for the study, enrolling 100 patients in 27 sites across the U.S.

"Sermonix selected Linical Accelovance to be our clinical research development partner for this program because we are impressed with the organization’s integrated clinical trial services, as well as its operational capabilities in the development of oncology drugs," said Sermonix Chief Operating Officer Dr. Miriam Portman.

The trial will utilize oral lasofoxifene for advanced breast cancer patients with ESR1 gene mutations. The primary clinical endpoint will be progression-free survival (PFS).

"Sermonix is developing lasofoxifene as a personalized medicine treatment for patients with ER+ metastatic breast cancer that have progressed after endocrine and other therapies," said Sermonix Chief Executive Officer Dr. David Portman. "We look forward to seeing how it performs in the Phase 2 trial versus fulvestrant."

About Lasofoxifene

Lasofoxifene is an investigational, nonsteroidal selective estrogen receptor modulator (SERM), which Sermonix licensed from Ligand Pharmaceuticals Inc. (NASDAQ: LGND). Lasofoxifene has been studied in comprehensive non-oncology clinical trials recruiting more than 15,000 women worldwide and has demonstrated efficacy for treating vulvovaginal atrophy (VVA), and postmenopausal osteoporosis.

Oral Lasofoxifene’s binding affinity and activity in mutations of the estrogen receptor may hold promise for patients who have acquired resistance and mutations of the estrogen receptor, a common mutation in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations has recently been discovered and Sermonix has exclusive rights to develop and commercialize oral lasofoxifene in this area. Oral Lasofoxifene, a potent, well-tolerated and bioavailable SERM, if approved could play a critical role in the personalized treatment of advanced ER+ breast cancer.

Constellation Pharmaceuticals Enhances and Expands Phase 2 MANIFEST Study of CPI-0610 in Myelofibrosis

On October 10, 2018 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported several planned updates to the Phase 2 portion of its ongoing MANIFEST study, an open-label Phase 1/2 clinical trial of its BET inhibitor CPI-0610 in MF (Press release, Constellation Pharmaceuticals, OCT 10, 2018, View Source [SID1234530620]).

MANIFEST is evaluating CPI-0610, either as a monotherapy or in combination with ruxolitinib, in patients with MF who are refractory or intolerant or have relapsed or lost response to the standard of care. Based on encouraging preliminary data in this trial, Constellation is amending the design of each second-line cohort to stratify all patients enrolled in the study based on transfusion dependence status. In addition, the Company is amending the design of MANIFEST to include a third cohort designed to evaluate treatment with CPI-0610 in combination with ruxolitinib as a first-line therapy in JAK 1/2-inhibitor-naïve MF patients.

The Company made these updates based on the unmet medical need for disease-modifying therapies in myelofibrosis, especially among patients requiring red-blood-cell transfusions. The changes are intended to enhance the clinical trial design by providing additional measures of potential clinical benefit and to expand the potential addressable patient population for CPI-0610.

"We are encouraged by the preliminary data from MANIFEST, which may indicate synergistic and disease-modifying effects of CPI-0610 in myelofibrosis," said Adrian Senderowicz, Senior Vice President and Chief Medical Officer of Constellation Pharmaceuticals. "We are enhancing the study’s design to better measure these potential effects. Among the key goals of MANIFEST are identifying the most appropriate endpoints and patient populations for future pivotal studies. We continue to look forward to determining proof of concept for CPI-0610 in MF by mid-2019."

MANIFEST Enhancements

The Phase 2 proof-of-concept portion of MANIFEST in a second-line setting is designed to study the anti-tumor activity and safety of the BET inhibitor CPI-0610 in treatment of patients with MF as a monotherapy and in combination with the JAK-1/2 inhibitor ruxolitinib. This portion of the study had been expected to enroll 70 patients (35 on monotherapy and 35 on combination therapy) to evaluate safety, pharmacokinetics, reduction in spleen volume, and patient-reported symptom improvement in all enrolled patients, as well as improvements in red-blood-cell transfusion independence rate in patients who were transfusion-dependent at baseline. Preliminary data from this trial demonstrated spleen volume reduction, symptom improvement, and positive hemoglobin effects, which Constellation believes may be the result of improved hematopoiesis. In addition, as Constellation reported previously, one of four patients treated with CPI-0610 was transfusion-dependent at baseline and later converted to transfusion independence.

As a result of this positive preliminary hematological data, all enrolled patients in both the combination and monotherapy arms will now be stratified by transfusion dependence status, with each cohort expected to enroll up to 16 transfusion-dependent patients and up to 25 non-transfusion-dependent patients. Proof of concept in these cohorts will be based on conversion to transfusion independence and other factors in transfusion-dependent patients; and by reduction in spleen volume, patient-reported symptom improvement, and other factors in non-transfusion-dependent patients.

In addition, Constellation is adding a third cohort to this trial, which will evaluate treatment with CPI-0610 in combination with ruxolitinib as first-line therapy in up to 43 JAK 1/2-inhibitor-naïve MF patients. This cohort will only enroll anemic patients. Constellation’s current plan for a potential pivotal trial of CPI-0610 as a first-line treatment would be to enroll all-comers. Proof of concept for this cohort will be measured by reduction in spleen volume, patient-reported symptom improvement, and other factors.

The Company expects to update this protocol change at View Source under study ID NCT02158858 in the near future.

Conference Call/Corporate Presentation

Constellation’s CEO Jigar Raythatha and CMO Adrian Senderowicz will host a conference call to discuss this protocol change in greater detail at 8:30 AM EDT on Thursday, October 11. To participate in the conference call, please dial (877) 473-2077 (US) or +1(661) 378-9662 (international) and refer to conference ID 4165317. A live webcast will be available in the investor section of the company’s website. The webcast will be archived for 60 days following the call. Constellation has posted an updated version of its corporate presentation in the investor section of the company’s website.

Hemispherx Biopharma Signs Clinical Trial Agreement with Roswell Park Comprehensive Cancer Center to Study Ampligen in Combination with Checkpoint Inhibitors in a Phase IIa Study in Urothelial Carcinoma, Renal Cell Carcinoma and Melanoma

On October 10, 2018 Hemispherx Biopharma, Inc. (NYSE American: HEB) reported the signing of a clinical trial agreement with Roswell Park Comprehensive Cancer Center to evaluate Ampligen in combination with checkpoint inhibitors (CPIs) (Press release, Hemispherx Biopharma, OCT 10, 2018, View Source [SID1234530604]). The Phase IIa clinical trial will evaluate the immune-mediated effects of cytokine modulation in combination with CPIs in patients with primary resistance to CPI therapy. The protocol will seek to evaluate the combination of Ampligen and CPIs in patients with advanced urothelial carcinoma, renal cell carcinoma and melanoma. Ampligen is the Company’s investigational immune-enhancing TLR3 agonist that has demonstrated a robust anti-cancer effect in preclinical models when combined with CPIs. This new agreement expands the extensive prior clinical and preclinical work into the clinical checkpoint blockade arena and offers the opportunity to begin evaluation of this combination therapy in patients with a variety of solid tumors where large numbers of patients do not respond or progress following treatment with standard CPI-based therapy.

The Phase IIa study will be led by Pawel Kalinski, MD, PhD, Vice Chair for Translational Research and Professor of Oncology in the Department of Medicine and Co-Leader of the Tumor Immunology and Immunotherapy Program at Roswell Park, in collaboration with Mateusz Opyrchal, MD, PhD, of the Roswell Park Department of Medicine. Additional details about trial design, implementation and timing will be disclosed upon approval by Roswell Park’s institutional review board.

"This event marks an important milestone for Hemispherx as we evaluate Ampligen in combination with CPIs in difficult-to-treat solid tumors and among a patient population that is largely relapsed and/or refractory to treatment," said Thomas K. Equels, Chief Executive Officer of Hemispherx. "Our expanded collaboration with Roswell Park offers an ideal setting for these early stage trials. We have developed a productive working relationship with this world-class team and look forward to beginning these important clinical trials."

Helix BioPharma Corp. and Moffitt Cancer Center extend collaboration on immunotherapy, including study of L-DOS47 with PD-1/PD-L1 inhibitors

On October 10, 2018 Helix BioPharma Corp. (TSX: HBP), (FSE: HBP) ("Helix" or the "Company"), an immuno-oncology company developing innovative drug candidates for the prevention and treatment of cancer, reported that it has extended its collaboration agreement with Moffitt Cancer Center for an additional year (Press release, Helix BioPharma, OCT 10, 2018, View Source [SID1234530409]).

During the first year of the collaboration, a new pancreatic adenocarcinoma mouse model suitable for testing L-DOS47 in combination with immunotherapy was developed. Preliminary studies in this model showed that L-DOS47 may increase the activity of a PD-1/PD-L1 inhibitor in treating pancreatic cancer. In addition, work was initiated to demonstrate that certain imaging techniques may be useful in directly measuring tumor acidity. Helix is hoping to use this non-invasive technique in the clinic soon.

In year two of the project, work will include not only the study of L-DOS47 in combination with PD-1/PDL1 inhibitors, but also in combination with other drugs in the pancreatic model. Analysis of the immune response that is occurring in the tumor upon L-DOS47 combination treatment will also be characterised. Results from these studies will add to the current understanding of how tumor acidity affects the tumor immune response. Data from these studies will also support Helix’s plan to increase the clinical application of L-DOS47 with various combination treatments, including immunotherapies with checkpoint inhibitors.

"We are strongly encouraged by our preliminary data that this may be an effective approach to improving outcomes to a variety of therapies" said Dr. Robert Gillies, Martin Silbiger Endowed Chair, Moffitt Cancer Center. "We know that tumor acidity is an important contributor to therapy resistance, and thus neutralizing acidity with L-DOS47 should have a positive effect in combination with chemotherapies and immune checkpoint blockade".

"This years’ Nobel prize in Physiology or Medicine was awarded for the discovery of cancer therapy by inhibition of negative immune regulation." said Heman Chao, Ph.D., Chief Executive & Scientific Officer of Helix. "We are very excited to work with the Moffitt team in applying L-DOS47 in immunotherapy and we look forward to using L-DOS47 with PD-1/PD-L1 inhibitors in the clinic which could result in significant benefits to patients."