On February 14, 2019 Forbius, a clinical-stage company that develops biologics for the treatment of cancer and fibrosis, reported a collaboration agreement with the Icahn School of Medicine at Mount Sinai and the Myeloproliferative Neoplasm Research Consortium (MPN-RC) (Press release, Forbius, FEB 14, 2019, View Source [SID1234533334]). This collaboration will launch an investigator-initiated trial (IIT) evaluating AVID200, a highly potent and isoform-selective TGF-beta inhibitor, as a potential treatment for myelofibrosis (MF). The Phase 1/2 clinical trial will be sponsored by the MPN-RC with NIH grant support and is expected to start during Q1 2019.

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"We have demonstrated that blocking TGF-beta signaling reverses bone marrow fibrosis and restores hematopoiesis in preclinical models. We believe that selective TGF-beta inhibition by AVID200 could address the underlying cause of bone marrow failure and become the first disease-modifying therapy in MF. Our consortium is eager to commence evaluation of AVID200 in the upcoming clinical study," commented Dr. Ronald Hoffman, founder of the MPN-RC and Director of the Myeloproliferative Disorders Research Program at the Icahn School of Medicine at Mount Sinai.

Forbius is evaluating the immuno-oncology and anti-fibrotic effects of AVID200 in Phase 1 trials, including solid tumors and systemic sclerosis. Additionally, Forbius is expanding the AVID200 clinical development program by supporting IITs through the provision of drug, scientific input, and collaboration on the conduct of translational studies. Additional details pertaining to the prospective IIT in MF will be disclosed in due course.

About the Myeloproliferative Neoplasm Research Consortium (MPN-RC)

The MPN-RC was founded in 2006 and is the only independent, multi-center, international consortium of scientists and clinicians that is dedicated to developing novel therapeutic strategies for MF and other myeloproliferative neoplasms (MPN). The MPN-RC is funded by the NIH to conduct clinical trials based on the most promising preclinical MPN research. The goal of the consortium is to adapt quickly in response to scientific advances and a changing clinical landscape, in order to develop effective therapeutics for MPN patients.

About AVID200

AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 & 3, the two principal pro-fibrotic TGF-beta isoforms. These TGF-beta isoforms are central regulators in the pathogenesis and progression of fibrotic diseases, including MF (Chagraoui et al., 2002). AVID200 was rationally designed to be minimally active against TGF-beta 2, which is a promoter of hematopoiesis and normal cardiac function. This optimal selectivity positions AVID200 to be an effective and well-tolerated therapeutic in MF and other fibrotic diseases.

About Myelofibrosis (MF)

MF is a rare, life-threatening blood cancer characterized by progressive bone marrow fibrosis, which causes ineffective hematopoiesis. Approximately 30,000 people in the US alone are affected by this disease. Currently, there are no approved therapies targeting the underlying bone marrow fibrosis available to MF patients.

On February 14, 2019 Tanabe Research Laboratories U.S.A. Inc. (TRL), a subsidiary of Mitsubishi Tanabe Pharmaceutical Corporation, is a California based research, development and clinical stage company specializing in antibody technologies to treat cancer and other diseases with unmet medical needs (Press release, Mitsubishi Tanabe Pharma, FEB 14, 2019, View Source [SID1234533335]). TRL announced today that the U.S. Food and Drug administration (FDA) accepted the company’s first Investigational New Drug (IND) application to initiate a phase I trial for its Antibody Drug Conjugate TR1801-ADC (MT- 8633) in patients with cMet positive solid tumors.

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"We are excited to be able to move TR1801-ADC into the clinic," said Roland Newman, TRL’s Chief Scientific Officer. "TR1801-ADC is an extremely potent ADC that combines a non-agonizing anti-c-Met antibody developed at TRL, with a pyrrolobenzodiazepine dimer (PBD) toxin, and has demonstrated potent dose dependent anti-tumor activity against Met positive tumors in preclinical models."

The PBDs were developed by TRL’s collaborative partner MedImmune, the global biologics research and development arm of AstraZeneca (LSE: AZN), via its proprietary Spirogen technology and licensed to TRL. PBDs are of an order of magnitude more potent than other warheads currently used with other ADCs, and in the case of TR1801-ADC are linked to the antibody via a site-specific conjugation site.

cMet, also referred to as the hepatic growth factor receptor (HGFR), is a validated target expressed on a variety of tumor types including colorectal, NSCLC, gastric, esophageal, pancreatic, bile duct and many other cancers. "Patients will be selected based on c-Met expression levels using a histological screening system (IHC) to determine their eligibility. Patients that have either cMet gene amplification or are non-gene amplified will both be eligible for the trial as long as they meet the IHC expression cutoff requirement," said Gary Woodnutt, TRL’s VP of Development.

"The acceptance of this IND by the FDA is an important milestone for TRL," said CEO and President Naoki Sakurai, "as it validates our research efforts and represents the first ADC product in a rich future pipeline. This achievement is a result of hard work by our dedicated employees and is the first drug in TRL’s mission of creating therapies with a meaningful clinical benefit for patients."

About TRL:

TRL is an independent subsidiary of MTPC located in San Diego California, whose role is to discover and develop biological drug candidates for therapy. Currently, TRL’s efforts are directed towards antibody-related research to target tumors and other diseases with high unmet needs. TRL has established collaborative relationships with other companies and academic research organizations to develop Antibody Drug Conjugates (ADCs) and to identify therapeutic lead compounds for development. View Source

On February 14. 2019 Evelo Biosciences, Inc. (Nasdaq: EVLO) ("Evelo"), a clinical stage biotechnology company developing monoclonal microbials, a potential new modality of oral biologic medicines, reported financial results and provided a business update for the fourth quarter and full year 2018 (Press release, Evelo Biosciences, FEB 14, 2019, View Source [SID1234533299]).

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"Our platform opens up the potential for effective, orally delivered, safe and cost-effective medicines for improved treatments of inflammatory diseases and cancers. In 2018, we made significant progress and advanced our first three product candidates into clinical trials across multiple inflammatory diseases and cancers," said Simba Gill, Ph.D., president and chief executive officer of Evelo. "In 2019, we expect to advance our oncology clinical trials and announce clinical data from our ongoing inflammatory disease clinical trials which may signal the potential for monoclonal microbials as a broadly applicable new modality of medicines."

2018 and Recent Business Highlights:

Inflammation

April 2018 – Evelo initiated a placebo-controlled Phase 1b clinical trial of EDP1066 in healthy volunteers and patients with atopic dermatitis or psoriasis. Following completion of each of the three dose-ascending healthy volunteer cohorts, data was reviewed by the trial’s safety review committee and the trial proceeded as planned into cohorts of patients with atopic dermatitis or psoriasis

November 2018 – Evelo initiated a placebo-controlled Phase 1b clinical trial of EDP1815 in healthy volunteers and patients with atopic dermatitis or psoriasis

Oncology

November 2018 – Entered into clinical collaboration with Merck to evaluate EDP1503 in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in multiple cancer indications

December 2018 – Evelo initiated an open-label Phase 1/2 clinical trial of EDP1503 in combination with KEYTRUDA in microsatellite stable colorectal cancer, triple-negative breast cancer, and patients with other tumor types that have relapsed on prior PD-1/L1 inhibitor treatment

January 2019 – The University of Chicago initiated an open-label Phase 2a clinical trial of EDP1503 in combination with KEYTRUDA in naïve melanoma patients and melanoma patients that have relapsed on prior PD-1/L1 inhibitor treatment

Non-Replicating Monoclonal Microbials

Preclinical studies have shown that non-replicating monoclonal microbials, which have been treated to prevent growth and division, maintain activity, opening up the potential to develop non-replicating monoclonal microbial clinical candidates

Monoclonal microbial activity is likely driven by recognition of structural motifs by immune cells in the small intestine and is not dependent on engraftment or colonization

Nominated EDP1867 as a preclinical monoclonal microbial candidate for inflammatory diseases. EDP1867 is the first monoclonal microbial specifically developed as a non-replicating product candidate in Evelo’s pipeline

Anticipated 2019 Clinical Milestones

Initial clinical data from the ongoing Phase 1b clinical trial of EDP1066 in healthy volunteers and patients with psoriasis or atopic dermatitis in the second quarter of 2019

Initiation of an immuno-pharmacology clinical study in healthy volunteers with EDP1066 in 1H 2019, designed to explore additional doses and formulations ahead of potential later stage trials.

Initial clinical data from the ongoing Phase 1b clinical trial of EDP1815 in healthy volunteers and patients with psoriasis or atopic dermatitis in the second half of 2019

Initiation of clinical trials with EDP1066 and EDP1815 in additional inflammatory disease indications in the second half of 2019

Fourth Quarter and Full Year 2018 Financial Results

Cash Position: As of December 31, 2018, cash, cash equivalents and investments were $147.9 million, as compared to cash and cash equivalents of $38.2 million as of December 31, 2017. This increase was due to net proceeds of $81.3 million from the issuance of Series C convertible preferred stock, net proceeds of $75.8 million from Evelo’s initial public offering and $5.0 million of additional drawings from Evelo’s existing debt facility, partially offset by cash used to fund operating activities for the full year 2018. Evelo expects that its cash, cash equivalents and investments will enable it to fund its planned operating expenses and capital expenditure requirements into the second half of 2020.

Research and Development Expenses: R&D expenses were $11.3 million for the three months ended December 31, 2018 and $39.9 million for the full year ended December 31, 2018, compared to $6.1 million for the three months ended December 31, 2017 and $20.0 million for the full year ended December 31, 2017. The increase of $19.9 million for 2018 was due primarily to increases in costs related to Evelo’s inflammation and oncology clinical development programs, and gut-body network platform expenses, as well as increased personnel costs.

General and Administrative Expenses: G&A expenses were $4.7 million for the three months ended December 31, 2018 and $18.2 million for the full year ended December 31, 2018, compared to $2.0 million for the three months ended December 31, 2017 and $7.6 million for the full year ended December 31, 2017. The increase of $10.6 million for 2018 was due primarily to increased general and administrative personnel costs, professional and consulting fees, and facility expenses supporting Evelo’s growing organization and public company infrastructure.

Net Loss Attributable to Common Stockholders: Net loss attributable to common stockholders was $15.4 million for the three months ended December 31, 2018 and $60.9 million for the full year ended December 31, 2018, or $(0.49) and $(2.78) per basic and diluted share, respectively, as compared to a net loss attributable to common stockholders of $9.9 million for the three months ended December 31, 2017 and $34.1 million for the full year ended December 31, 2017,or $(2.57) and $(9.10) per basic and diluted share, respectively.

Conference Call
Evelo will host a conference call and webcast today at 8:30a.m. ET. To access the call please dial (866) 795-3242 (domestic) and (409) 937-8909 (international) and provide the passcode 7986199. A live webcast of the call will be available on the Investors sections of the Evelo website at www.evelobio.com. The archived webcast will be available approximately two hours after the conference call and will be available for 30 days following the call.

On February 14, 2019 Verastem, Inc. (Nasdaq:VSTM) (Verastem Oncology or the Company), a biopharmaceutical company focused on developing and commercializing medicines seeking to improve the survival and quality of life of cancer patients, reported that the results of the Phase 2 DYNAMO study, which evaluated COPIKTRA (duvelisib) capsules in patients with indolent non-Hodgkin lymphoma (iNHL) who were refractory to both rituximab and chemotherapy or radioimmunotherapy, was published online in the [peer-reviewed] Journal of Clinical Oncology (Press release, Verastem, FEB 14, 2019, View Source;p=RssLanding&cat=news&id=2387473 [SID1234533319]). COPIKTRA received accelerated approval from the U.S. Food and Drug Administration on September 24, 2018 for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. Additionally, COPIKTRA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) after at least two prior therapies.

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COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), a dual inhibitor of both PI3K-delta and PI3K-gamma. The COPIKTRA New Drug Application (NDA) was supported by clinical data from the open-label, single-arm Phase 2 DYNAMO study (NCT01882803), which evaluated the efficacy and safety of COPIKTRA (25mg twice daily) as a monotherapy in 129 adult patients with various types of iNHL, including follicular lymphoma (FL; n=83), small lymphocytic lymphoma (SLL; n=28) or marginal zone lymphoma (MZL; n=18), whose disease had progressed and who were refractory to rituximab and to either chemotherapy or radioimmunotherapy. The primary endpoint of the study was ORR as assessed by an independent review committee (IRC).

"Indolent non-Hodgkin lymphoma remains largely incurable and often requires multiple lines of treatment after becoming refractory to standard therapies," said Ian Flinn, M.D., Ph.D., Director of the Lymphoma Research Program at Sarah Cannon Research Institute, lead investigator of the Phase 2 DYNAMO study and lead author of the manuscript. "In the DYNAMO study, oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, double-refractory iNHL, including in patients with SLL, FL and MZL. Duvelisib is an important addition to the evolving treatment paradigm for patients with FL and we are delighted to have the study results published in this prestigious journal to share with the medical and scientific communities."

While MZL patients were included in the DYNAMO study, COPIKTRA has not been deemed safe and effective by the FDA for use in treating patients suffering from MZL, however, MZL represents a potential new patient indication that may benefit from COPIKTRA.

The National Comprehensive Cancer Network (NCCN) has added COPIKTRA to the Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL, FL and MZL. The NCCN Guidelines are the standard physician resource for determining the appropriate course of treatment for patients.

The full manuscript, titled "DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma," (Flinn, et al. DOI: 10.1200/JCO.18.00915) can be accessed here.

Results of the Phase 2 DYNAMO Study in iNHL

The ORR per IRC-assessed response was 47% (95% CI, 38% to 56%). The study met its primary end point (p<0.001). ORR per IRC was 42%, 68%, and 39% in FL, SLL, and MZL subtypes, respectively. Responses were rapid and durable. Median time to response (TTR) was 1.87 months (range, 1.4 to 11.7 months), with 59% and 84% of patients responding by 2 and 4 months, respectively. Median duration of response (DOR) was 10 months (95% CI, 6.5 to 10.5 months), with estimated probabilities of remaining in response at 6 and 12 months of 69% and 35%. Median PFS was 9.5 months (95% CI, 8.1 to 11.8 months), with the probability of surviving and being progression free at 6 months estimated at 62%. Median overall survival (OS) was 28.9 months (95% CI, 21.4 months to not estimable), and OS at 1 year was estimated at 77%. Among the 39 patients with FL who received an R-CHOP (or equivalent) chemoimmunotherapy regimen as first therapy, 30 (77%) experienced early relapse (no response during treatment or progressive disease or time to next treatment less than 2 years). This patient subgroup showed an ORR of 33%, median DOR of 12.6 months and median PFS of 8.2 months. The approval and corresponding label of COPIKTRA in FL was based on the efficacy and safety results from the FL patients (n=83) in DYNAMO that had received at least two prior systemic therapies. The accelerated approval was based on overall response rate (ORR) and continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. COPIKTRA is not FDA approved for MZL.

COPIKTRA contains a BOXED WARNING for four fatal and/or serious toxicities: infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. More information about these Boxed Warnings and additional Important Safety Information can be found below and in the full Prescribing Information at www.COPIKTRA.com.Verastem Oncology is implementing a Risk Evaluation and Mitigation Strategy to provide appropriate dosing and safety information to better support physicians in managing their patients on COPIKTRA.

COPIKTRA is associated with adverse reactions which may require dose reduction, treatment delay or discontinuation of COPIKTRA. In addition to the BOXED WARNING, COPIKTRA has WARNINGS AND PRECAUTIONS for hepatotoxicity, neutropenia, and embryo-fetal toxicity. The most common ADVERSE REACTIONS (reported in ≥ 20% of patients) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.

Please see important Safety Information provided below and Prescribing Information including BOXED WARNING and Medication Guide at www.COPIKTRAHCP.com/prescribinginformation

About Follicular Lymphoma

Follicular lymphoma (FL) is typically a slow-growing or indolent form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes, making it a B-cell lymphoma. This lymphoma subtype accounts for 20 to 30 percent of all NHL cases, with more than 140,000 people in the US with FL and more than 13,000 newly diagnosed patients this year. Common symptoms of FL include enlargement of the lymph nodes in the neck, underarms, abdomen, or groin, as well as fatigue, shortness of breath, night sweats, and weight loss. Often, patients with FL have no obvious symptoms of the disease at diagnosis. Follicular lymphoma is usually not considered to be curable, but more of a chronic disease, with patients living for many years with this form of lymphoma. The potential of additional oral agents, particularly as a monotherapy that can be used in the general community physician’s armamentarium, may hold significant value in the treatment of patients with FL.

About COPIKTRA (duvelisib)

COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies and relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. COPIKTRA is also being developed by Verastem Oncology for the treatment of peripheral T-cell lymphoma (PTCL), for which it has received Fast Track status, and is being investigated in combination with other agents through investigator-sponsored studies.4 For more information on COPIKTRA, please visit www.COPIKTRA.com. Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

On February 14, 2019 Scientific teams from NantHealth (NASDAQ: NH) and NantOmics reported that it will present two posters at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium this week (Press release, NantHealth, FEB 14, 2019, View Source;p=RssLanding&cat=news&id=2387497 [SID1234533300]). The two companies, respective leaders in molecular profiling research and genomic testing solutions, teamed together to explore the significance of RNA expression and individual biomarkers in determining why some patients do not respond to targeted cancer therapies based on DNA genomic profiling alone.

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The first poster session will provide insights on individual biomarkers obtained from liquid biopsies that may potentially improve immune checkpoint therapies for prostate cancer. The second session will feature research, conducted with experts from the UC San Diego Health Moores Cancer Center, that demonstrates the benefits of examining discrepancies between DNA alterations and RNA expression that could be the cause of treatment failure for people with metastatic kidney, bladder, and prostate cancer.

"While next generation sequencing for advanced cancers has become routine, not all patients are responding to targeted treatments based solely on DNA genomic profiling," said Sandeep "Bobby" Reddy, MD, Chief Medical Officer, NantHealth. "It is becoming clear that we must delve deeper into RNA expression, as well as identify key biomarkers, to develop effective cancer treatments and therapies."

NantHealth and NantOmics will present the following posters at this year’s Genitourinary Cancers Symposium:

Concomitant characterization of androgen receptor (AC) and immune checkpoints (ICs) in cell-free (cf) DNA and RNA from patients with metastatic castration resistant prostate cancer (mCRPC) – 11:30AM-1:00PM & 5:30PM-6:30PM, 2/14/2019, Session A, Board M21, Abstract #286
RNA sequencing in addition to next generation sequencing in advanced genitourinary cancers reveals transcriptomic silencing of DNA mutations: Implications for resistance to targeted therapeutics – 7:00AM-7:55AM & 12:30PM-2:00PM, 2/16/2019, Session C, Board E22, Abstract #583
The 2019 Genitourinary (GU) Cancers Symposium is a three-day scientific and educational meeting in San Francisco designed to meet the needs of physicians and other members of the cancer care and research community who diagnose, treat, and study GU malignancies.