On June 18, 2018 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for its lead program, mirvetuximab soravtansine (Press release, ImmunoGen, JUN 18, 2018, View Source [SID1234527375]). The designation is for the treatment of patients with medium to high folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer who received at least one, but no more than three prior systemic treatment regimens, and for whom single-agent chemotherapy is appropriate as the next line of therapy.

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"We are pleased the FDA has granted Fast Track designation for mirvetuximab soravtansine," said Mark Enyedy, ImmunoGen’s President and Chief Executive Officer. "Patients with platinum-resistant ovarian cancer have a poor prognosis and we are encouraged by the FDA’s recognition of the significant need for new therapeutic options that may be addressed by mirvetuximab as monotherapy. This important designation is based on the promising safety and activity findings observed to-date and we look forward to working closely with the FDA as we advance the development of mirvetuximab."

The FDA’s Fast Track Designation is intended to facilitate development and expedite review of drugs to treat serious and life-threatening conditions so that an approved product can reach the market expeditiously.

Mirvetuximab soravtansine is being evaluated in the FORWARD I Phase 3 trial. The trial is designed to randomize 333 patients 2:1 to receive either mirvetuximab soravtansine or the physician’s choice of single-agent chemotherapy. Eligibility criteria include patients with platinum-resistant ovarian cancer that express medium or high levels of FRα who have been treated with up to three prior regimens. The primary endpoint of this study is Progression Free Survival, which is being assessed in the entire study population and in the subset of patients with high FRα expression. Enrollment of FORWARD I was completed ahead of schedule in April 2018 and ImmunoGen expects to report top-line results from the FORWARD I trial in the first half of 2019.

ImmunoGen is partnering with the Gynecologic Oncology Group Foundation Inc., a leader in clinical research in gynecologic malignancies, on FORWARD I, which is being conducted in North America and Europe. This trial is intended to support full marketing approval of mirvetuximab for patients with platinum-resistant ovarian cancer.

Mirvetuximab soravtansine is also being assessed in multiple combinations in the FORWARD II trial. FORWARD II is a Phase 1b/2 study of mirvetuximab in combination with Avastin (bevacizumab), or Keytruda (pembrolizumab) in patients with FRα-positive platinum-resistant ovarian cancer, primary peritoneal, or fallopian tube tumors, as well as a triplet combination of mirvetuximab plus carboplatin and Avastin in patients with platinum-sensitive ovarian cancer.

About Mirvetuximab Soravtansine

Mirvetuximab soravtansine (IMGN853) is the first folate receptor alpha (FRα)-targeting ADC. It uses a humanized FRα-binding antibody to target the ADC specifically to FRα-expressing cancer cells and a potent anti-tumor agent, DM4, to kill the targeted cancer cells.

About Ovarian Cancer and FRα

It is estimated that 22,000 women are diagnosed annually with ovarian cancer in the US. With more than 14,000 deaths each year, ovarian cancer accounts for more deaths than any other cancer of the female reproductive system.1

Standard first-line therapy for ovarian cancer is a platinum-based combination regimen. Once the cancer becomes platinum-resistant, treatment options include single-agent cytotoxic therapies such as pegylated liposomal doxorubicin, paclitaxel, or topotecan, and combination therapies that include Avastin.

There is a significant need for more effective, better-tolerated therapies for recurrent ovarian cancer. It is estimated that approximately 19,000 women in the US and approximately 24,000 women in the EU have platinum-resistant ovarian cancer requiring second-line or later treatment.2 ImmunoGen estimates that 60% of ovarian cancer cases have medium or high FRα expression.

On June 18, 2018 Crinetics Pharmaceuticals, Inc., a clinical stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors, reported the appointment of Alan S. Krasner, M.D. as Chief Medical Officer (Press release, Crinetics Pharmaceuticals, JUN 18, 2018, View Source [SID1234527377]).

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"We are delighted to welcome Alan to the Crinetics management team," said Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics. "Alan has extensive experience in clinical development of endocrine drugs at both big pharma and smaller biotech companies. We are fortunate to have his leadership to oversee our development programs as we advance our product candidates into and through the clinic."

Dr. Krasner joins Crinetics from Shire Pharmaceuticals where he was a Senior Medical Director and served as Global Development Lead for Natpara, the first recombinant human intact parathyroid hormone treatment for hypoparathyroidism. Prior to Shire, he worked at Biodel and Pfizer conducting clinical research at various stages of development in diabetes and obesity. He obtained his undergraduate and M.D. degrees from Northwestern University and received his clinical training in Internal Medicine and Endocrinology at Johns Hopkins University.

On June 18, 2018 TG Therapeutics, Inc. (NASDAQ: TGTX), reported an oral presentation of clinical data from its ongoing Phase 2 study evaluating umbralisib (TGR-1202), the Company’s PI3K delta inhibitor, in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) who are intolerant to prior BTK or PI3K delta inhibitor therapy (Press release, TG Therapeutics, JUN 18, 2018, View Source [SID1234527378]). Data from this trial were presented over the weekend during an oral session at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, stated, "We are pleased to present data evaluating umbralisib in patients intolerant to currently approved BTK or PI3K therapies during the EHA (Free EHA Whitepaper) annual congress. While there have been great advancements in recent years in the treatment of CLL, this study confirms that there are many patients still in need of an alternative treatment option and that umbralisib can be used safely and effectively in those patients who were not able to tolerate a prior BTK or PI3K therapy. The rate of patients withdrawing from kinase treatment for CLL in real world settings has been estimated to reach upwards of 40%, representing a significant unmet medical need." Mr. Weiss continued, "We are extremely pleased with the data presented at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) this month and we look forward to presenting the topline response rate data from the UNITY- CLL Phase 3 trial by the end of summer 2018."

Highlights from the oral presentation include the following:

Oral Presentation: A Phase 2 Study to Assess the Safety and Efficacy of Umbralisib (TGR-1202) In Patients with Chronic Lymphocytic Leukemia (CLL) Who Are Intolerant to Prior BTK or PI3K-delta Inhibitor Therapy (Abstract Number S808)

This presentation includes data from patients with CLL who are intolerant to prior BTK or PI3K delta inhibitor therapy who were then treated with single agent umbralisib (TGR-1202). To be eligible for the study patients had to have received prior treatment with a BTK inhibitor (ibrutinib, acalabrutinib) or a PI3K delta inhibitor (idelalisib, duvelisib) and discontinued therapy due to intolerance within 12 months of starting treatment on this study. Forty-seven patients were evaluable for safety of which 46 were evaluable for Progression Free Survival (PFS), (1 patient had a confirmed Richter’s Transformation (RT) at enrollment which did not meet eligibility criteria).

Highlights from this presentation include:

●Umbralisib demonstrated a favorable safety profile in patients intolerant to prior BTK or PI3K therapy

●Only 13% discontinued due to an adverse event, of which only one patient discontinued due to a recurrent adverse event (AE) also experienced with prior kinase inhibitor therapy

●Median progression free survival (PFS) and overall survival has not been reached with a median follow-up of 9.5 months

●In this relapsed/refractory CLL population, of which 77% required treatment within 6 months of prior KI discontinuation, 64% had a high-risk molecular / genetic marker and 6% had an ibrutinib resistance mutation, significant clinical activity has been observed

PRESENTATION DETAILS
The above referenced presentation is now available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

On June 18, 2018 NeuroVive Pharmaceutical AB and BridgeBio Pharma reported that BridgeBio has entered into an exclusive licensing agreement for a subset of succinate prodrug chemistry under NeuroVive’s NVP015 program (Press release, BridgeBio, JUN 18, 2018, View Source [SID1234576278]). BridgeBio also announced that it has launched a subsidiary company Fortify Therapeutics to further develop this chemistry for local treatment of Leber’s Hereditary Optic Neuropathy (LHON), with an initial financial commitment of $20 million USD. NeuroVive’s NVP015 program for other mitochondrial disorders will continue without any changes in focus or timelines.

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LHON is caused by mitochondrial DNA mutations in subunits of NADH dehydrogenase (complex I), leading to reduced oxidative phosphorylation and energy production in retinal cells. The disease predominantly affects young adults, and results in sudden onset of progressive and severe vision loss. The licensed succinate prodrugs have the potential to overcome the disease by bypassing the dysfunctional metabolic pathway, providing an alternate source of energy to the retinal cells.

"As a targeted treatment for a genetic disease, the LHON program is a clear fit with the BridgeBio model," said Neil Kumar, Ph.D., CEO of BridgeBio. "We have been impressed with the ability of these compounds to rescue specific genetic mitochondrial deficiencies, and we have assembled a team of international experts to further develop a subset of the NVP015 chemistry to address this devastating disease."

Fortify Therapeutics will develop selected lead compounds derived from NeuroVive’s novel NVP015 succinate prodrug program into drug candidates for the localized treatment of LHON. These compounds have been selected because they have properties that make them suitable for delivery to the eye.

The licensing agreement for this particular subset of the NVP015 program has a total deal value of approximately $60 million USD, which includes limited initial funding for research, and later milestone payments and a single digit royalty stream, that are dependent on successful development and market approval.

"The agreement with BridgeBio is important to both NeuroVive and our innovative NVP015 program, as it validates the quality of the program, our business development model and potential in a variety of mitochondrial disorders," commented NeuroVive CEO Erik Kinnman, M.D., Ph.D. "We will work closely with BridgeBio to further develop this chemistry subset and make the LHON program successful. It is important to note that our intentions for the NVP015 program are unchanged, and we are progressing towards experimental proof-of-principle during 2018."

This information is information that NeuroVive Pharmaceutical AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out below, at 08:30 a.m. CET on 18 June 2018.

About LHON
Leber’s Hereditary Optic Neuropathy (LHON) is a disease caused by mitochondrial DNA mutations in subunits of NADH dehydrogenase (complex I), a component of the electron transport chain. This results in dysfunctional oxidative phosphorylation and ATP production, leading to degeneration of the retinal ganglion cells and loss of central vision. LHON most commonly affects males in their second or third decade of life. The prevalence of LHON in Europe is between 1:30,000-1:50,000.

About NVP015
One of the most common causes of mitochondrial diseases relates to Complex I dysfunction, i.e. when energy conversion in the first of the five protein complexes in the mitochondrion that are essential for effective energy conversion does not function normally. This is apparent in disorders including Leigh’s Syndrome and MELAS, both of which are very serious diseases with symptoms such as muscle weakness, epileptic fits and other severe neurological manifestations. The NVP015 project is based on a NeuroVive innovation in which the body’s own energy substrate, succinate, is made available in the cell via a prodrug technology. A prodrug is an inactive drug that is activated first when it enters the body by the transformation of its chemical structure. Results from the NVP015 project were published in the prestigious Nature Communications journal in August 2016.

On June 18, 2018 Gamida Cell, a leading cellular and immune therapeutics company, reported that preliminary data from an ongoing phase I study from the nicotinamide-based natural killer cell expansion, or NAM-NK, program will be presented during the Inaugural AACR (Free AACR Whitepaper) International Meeting on Advances in Malignant Lymphoma, held June 22 – 26 in Boston, Massachusetts (Press release, Gamida Cell, 18 18, 2018, View Source [SID1234527379]).

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Veronika Bachanova, M.D., Ph.D., hematologist/oncologist at the Blood and Marrow Transplantation and Cellular Therapy Program of the University of Minnesota, and lead investigator of the investigator-sponsored phase I NAM-NK clinical study at the Masonic Cancer Center, will present a poster of early patient outcomes from the study in patients with refractory non-Hodgkin lymphoma and multiple myeloma.

Title: Phase I study of nicotinamide-expanded related donor Natural Killer (NK) cells for the treatment of relapsed/refractory CD20+ non-Hodgkin lymphoma (Abstract: B05)
Session: Poster Session B: Therapeutics and Clinical Trials in Lymphoma 2
Location: Salon F, Boston Marriott Copley Place
Date: Sunday June 24, 2018 11:45 AM – 1:45 PM

About NAM-NK
Gamida Cell applied the capabilities of its NAM-based cell expansion technology to highly functional NK cells to develop NAM-NK, an innate immunotherapy for the treatment of hematologic and solid tumors in combination with SoC antibody therapies. NAM-NK addresses key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture. NAM-NK is in phase I development (NCT03019666) through an investigator-sponsored trial in patients with refractory non-Hodgkin lymphoma and multiple myeloma.