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Jounce Therapeutics Announces Major Strategic Collaboration with Celgene Corporation to Develop Next-generation Immuno-oncology Therapies for Patients with Cancer

On July 19, 2016 Jounce Therapeutics, Inc., a company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers for patient enrichment, reported a global strategic collaboration with Celgene Corporation (NASDAQ:CELG) focused on developing and commercializing innovative immuno-oncology treatments for patients with cancer (Press release, Jounce Therapeutics, JUL 19, 2016, View Source [SID:SID1234515271]). The collaboration includes options on Jounce’s lead product candidate, JTX-2011, targeting ICOS, and up to four early-stage programs to be selected from a defined pool of B cell, T regulatory cell and tumor-associated macrophage targets emerging from the Jounce Translational Science Platform and an additional option to equally share a checkpoint immuno-oncology program. Post option exercise, Jounce will lead global development and U.S. commercialization for JTX-2011 and one additional collaboration program.

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"Jounce has built a unique immuno-oncology platform and pipeline with a focus on the development of novel cancer therapies matched to patient populations most likely to respond," said Robert Hershberg, M.D., Ph.D., chief scientific officer, Celgene. "This collaboration allows both companies to leverage broad capabilities in immuno-oncology to bring forward a new generation of product candidates for cancer patients."

"Celgene is the ideal partner to collaborate with Jounce to bring potentially transformational treatments to patients with cancer," said Richard Murray, Ph.D., chief executive officer, Jounce Therapeutics. "This partnership is of significant strategic value for Jounce. With Celgene as our partner, we can broaden our platform, advance our discovery programs and execute comprehensive clinical strategies, all in the context of our approach to bring the right immunotherapies to the right patient populations."

Under the terms of the collaboration, Jounce will receive an upfront payment of $225 million and a $36 million equity investment from Celgene. Jounce will also receive regulatory, development, and net sales milestone payments and tiered royalties on ex-U.S. sales. Aggregate payments for development, regulatory and commercial milestones could potentially be $2.3 billion in total across all programs reaching commercialization.

Celgene has the option to opt-in at defined stages of development across the programs. Following any opt-in, Celgene and Jounce will share U.S. profits and losses on all programs, as follows:

Jounce will retain a 60 percent U.S. profit share of JTX-2011, with 40 percent allocated to Celgene;
Jounce will retain a 25 percent U.S. profit share on the first additional program, with 75 percent allocated to Celgene;
Jounce and Celgene will equally share U.S. profits on up to three additional programs;
After opt-in, all development costs will be shared in a manner that is commensurate with product rights; and
Celgene will also receive exclusive ex-U.S. commercialization rights for each of the above programs, and Jounce is eligible to receive a royalty on any resulting ex-U.S. sales. Celgene and Jounce will equally share profits globally for the checkpoint program.

About JTX-2011
Jounce’s lead product candidate, JTX-2011, is a monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells that is believed to stimulate an immune response against a patient’s cancer. We are developing JTX-2011 to treat solid tumors as a single agent and in combination with other therapies. JTX-2011 is expected to enter the clinic in the second half of 2016.

Valeant and Progenics Announce FDA Approves RELISTOR® Tablets
for the Treatment of Opioid-Induced Constipation in Adults with
Chronic Non-cancer Pain

On July 19, 2016 Valeant Pharmaceuticals International, Inc. (NYSE & TSX: VRX) and Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX) reported that the U.S. Food and Drug Administration has approved RELISTOR (methylnaltrexone bromide) Tablets for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain(Press release, Progenics Pharmaceuticals, JUL 19, 2016, View Source [SID:1234513971]). Valeant expects to commence sales of RELISTOR Tablets in the U.S. in the third quarter of 2016.

"Opioid-induced constipation represents a long-lasting and potentially debilitating side effect of opioid therapy for millions of patients suffering from chronic pain," commented Joseph C. Papa, Chief Executive Officer of Valeant. "We believe Oral RELISTOR represents a new alternative treatment for OIC, and we look forward to introducing the more convenient oral formulation as soon as practicable."

"We are delighted that this milestone for RELISTOR has been achieved, and that patients suffering from OIC will have this new treatment option," said Mark Baker, Chief Executive Officer of Progenics. "We expect the market to be receptive to a more convenient oral tablet formulation of RELISTOR’s well-established subcutaneous preparation. We would like to thank, in particular, Dr. Tage Ramakrishna and Dr. Robert Israel of Valeant for their work over many years in the clinical development of RELISTOR."

"RELISTOR has a unique mechanism of action that binds to mu-opioid receptors without impacting the opioid-mediated analgesic effects on the central nervous system," said Richard L. Rauck, MD, Medical Director, Center for Clinical Research, President, Carolinas Pain Institute, President of the Sceptor Pain Foundation of which he is a founding member, and Immediate Past President of the World Institute of Pain. "This represents a true breakthrough in the treatment of OIC, and addresses a large and growing need in the field of pain management."

Today, the FDA approved RELISTOR Tablets (450 mg once daily) for the treatment of OIC in adults with chronic non-cancer pain. Previously, RELISTOR Subcutaneous Injection (12 mg and 8 mg) was approved in 2008 for the treatment of OIC in adults with advanced illness who are receiving palliative care and in 2014 for the treatment of OIC in adults with chronic non-cancer pain.

About the Phase 3 Clinical Trial of Oral RELISTOR for OIC in Chronic Non-Cancer Pain (NCP)

A randomized, double-blind, Phase 3 trial was conducted to evaluate once-daily dosing of 450 mg (n=200) methylnaltrexone (MNTX) tablets compared to placebo (n=201) in adults with chronic NCP. In the 450 mg treatment arm, MNTX tablets demonstrated statistically significant improvements in rescue-free bowel movement (RFBM) within 4 hours of administration over 28 days of dosing when compared to placebo treatment, achieving the primary endpoint. The 450 mg treatment group also achieved statistical significance for the first key secondary efficacy endpoint where a higher percentage of responders (i.e., had ≥3 RFBMs/week, with an increase of ≥1 RFBM/week from baseline for at least 3 of the 4 weeks) was observed with MNTX treatment as compared to placebo. Overall, efficacy of oral methylnaltrexone in this study was comparable to that reported in clinical studies of subcutaneous methylnaltrexone in subjects with chronic, non-cancer pain. The overall observed safety profile seen in patients treated with oral methylnaltrexone was comparable to placebo in this study.

Important Safety Information about RELISTOR

RELISTOR (methylnaltrexone bromide) Tablets is contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.

Cases of gastrointestinal perforation have been reported in adult patients with OIC and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom.

If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider.

Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR.

Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia. Take into account the overall risk-benefit profile when using RELISTOR in such patients. Monitor for adequacy of analgesia and symptoms of opioid withdrawal in such patients.

Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.

The most common adverse reactions (≥ 12%) in adult patients with opioid-induced constipation and chronic non-cancer pain receiving RELISTOR tablets were abdominal pain, diarrhea, headaches, abdominal distention, hyperhidrosis, anxiety, muscle spasms, rhinorrhea, and chills. Adverse reactions of abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal.

Please see complete Prescribing Information for RELISTOR at valeant.com. For more information about RELISTOR, please visit www.relistor.com.

About RELISTOR

Progenics has exclusively licensed development and commercialization rights for its first commercial product, RELISTOR, to Valeant. RELISTOR Tablets (450 mg once daily) is approved in the United States for the treatment of OIC in patients with chronic non-cancer pain. RELISTOR Subcutaneous Injection (12 mg and 8 mg) is a treatment for opioid-induced constipation approved in the United States and worldwide for patients with advanced illness and chronic non-cancer pain.

Updated Data for Epacadostat, Incyte’s Selective IDO1 Inhibitor, Accepted for Presentation at the ESMO Annual Congress 2016

On July 19, 2016 Incyte Corporation (Nasdaq:INCY) reported that updated data from the Phase 1 portion of the ECHO-202/KEYNOTE-037 trial has been accepted for a poster discussion at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress 2016, taking place in Copenhagen, Denmark from October 7-11, 2016 (Press release, Incyte, JUL 19, 2016, View Source;p=RssLanding&cat=news&id=2186358 [SID:1234513958]). The ECHO-202 study (NCT02178722) is evaluating the safety and efficacy of epacadostat, Incyte’s selective IDO1 inhibitor, in combination with Keytruda (pembrolizumab)*, Merck’s anti-PD-1 therapy.

Poster details:
Epacadostat Plus Pembrolizumab in Patients With Advanced Melanoma and Select Solid Tumors: Updated Phase 1 Results From ECHO-202/KEYNOTE-037 (Abstract #1110PD)
Monday, 10 October 2016 from 11:00-12:00 CET
Full session details and data presentation listings for ESMO (Free ESMO Whitepaper) 2016 can be found at View Source

About Epacadostat (INCB024360)
Indoleamine 2,3-dioxygenase 1 (IDO1) is a key immunosuppressive enzyme that modulates the anti-tumor immune response by promoting regulatory T cell generation and blocking effector T cell activation, thereby facilitating tumor growth by allowing cancer cells to avoid immune surveillance. Epacadostat is a first-in-class, highly potent and selective oral inhibitor of the IDO1 enzyme that reverses tumor-associated immune suppression and restores effective anti-tumor immune responses. In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma. In these studies, epacadostat combined with the CTLA-4 inhibitor ipilimumab or the PD-1 inhibitor pembrolizumab improved response rates compared with studies of the immune checkpoint inhibitors alone. A Phase 3 study, ECHO-301, evaluating the combination of epacadostat with the anti-PD-1 antibody pembrolizumab for the first-line treatment of patients with advanced or metastatic melanoma has recently been initiated. Ongoing Phase 1 and Phase 2 studies are investigating epacadostat in combination with PD-1 and PD-L1 inhibitors in a variety of other cancer histologies

Cerulean Receives FDA Fast Track Designation for CRLX101 for the Treatment of Platinum-Resistant Ovarian Cancer

On July 19, 2016 Cerulean Pharma Inc. (NASDAQ:CERU), a clinical-stage company developing nanoparticle-drug conjugates (NDCs), reported that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for Cerulean’s lead nanoparticle-drug conjugate, CRLX101, in combination with paclitaxel, for the treatment of platinum-resistant ovarian carcinoma, fallopian tube or primary peritoneal cancer (Press release, Cerulean Pharma, JUL 19, 2016, View Source [SID:1234513963]).

"We appreciate the FDA’s acknowledgement of CRLX101’s potential in an area of significant unmet medical need," said Christopher D. T. Guiffre, President and Chief Executive Officer of Cerulean. "We are encouraged by the profound treatment effect observed early in the ongoing clinical trial with the GOG Foundation, Inc. (GOG), and we look forward to working closely with the FDA as we endeavor to bring a new treatment option to women living with platinum-resistant ovarian cancer."

CRLX101 is being evaluated in combination with weekly paclitaxel for the treatment of recurrent platinum-resistant ovarian carcinoma in a Phase 1b/2 clinical trial. Data from the Phase 1b portion of the trial were the subject of an oral presentation at the Gynecologic Oncology 2016 Conference in May. These data showed that five of the first nine patients (56%) enrolled in the trial achieved partial responses. Of note, five of the nine patients enrolled in the Phase 1b trial previously failed Avastin (bevacizumab) and three of these five patients achieved partial responses. Cerulean is conducting this trial in collaboration with the GOG and expects to provide an update at the European Society for Medical Oncology 2016 Congress.

In 2015, CRLX101 was granted Orphan Drug designation for the treatment of ovarian cancer.

The FDA’s Fast Track Program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious conditions and that demonstrate the potential to address unmet medical needs. Drugs that receive this designation benefit from more frequent communications and meetings with FDA to review the drug’s development plan, including the design of the proposed clinical trials and the extent of data needed for approval.

About CRLX101

CRLX101 is a nanoparticle-drug conjugate (NDC) designed to concentrate in tumors and slowly release its anti-cancer payload, camptothecin, inside tumor cells. CRLX101 inhibits topoisomerase 1 (topo 1), which is involved in cellular replication, and also inhibits hypoxia-inducible factor-1α (HIF-1α), which research suggests is a master regulator of cancer cell survival mechanisms. CRLX101 has shown activity in four different tumor types, both as monotherapy and in combination with other cancer treatments. CRLX101 is in Phase 2 clinical development and has been dosed in more than 350 patients. The U.S. FDA has granted CRLX101 Orphan Drug designation for the treatment of ovarian cancer, Fast Track designation in combination with paclitaxel for platinum-resistant ovarian carcinoma, fallopian tube or primary peritoneal cancer, and Fast Track designation in combination with Avastin in metastatic renal cell carcinoma.

Arbutus Reports Topline Results from TKM-PLK1 HCC Clinical Trial

On July 19, 2016 Arbutus Biopharma Corporation (Nasdaq:ABUS), an industry-leading hepatitis B virus (HBV) therapeutic solutions company, reported topline results from the completed Phase I/II TKM-PLK1 clinical study in patients with advanced Hepatocellular Carcinoma (HCC). Arbutus intends to explore partnership opportunities to enable further study of TKM-PLK-1 in HCC (Press release, Arbutus Biopharma, JUL 19, 2016, View Source [SID:1234513962]).

Arbutus today reported the following topline results from the Phase I/II study of TKM-PLK1 in HCC:

TKM-PLK1 was well-tolerated at all dose levels;
51% of subjects showed overall stable disease (SD) according to RECIST criteria;
22% of subjects showed an overall partial response (PR) according to Choi response criteria;
Tumor density reduction of up to 59% was observed;
"We are encouraged by the results from the TKM-PLK1 clinical trial in HCC patients and believe it supports further evaluation of this candidate as a potential treatment for HCC," said Dr. Mark Kowalski, Arbutus’ Chief Medical Officer. "The observed radiographic tumor density changes are consistent with tumor necrosis in a significant proportion of subjects, warranting further study of TKM-PLK1 for HCC, alone and in combination with other therapies."

"We are very pleased to report the positive results of this study of TKM-PLK1 in HCC, which we view as further validation of our capability to develop promising product candidates using our proprietary LNP delivery technology," said Dr. Mark J. Murray, Arbutus’ President and CEO. "Given Arbutus’ focus on HBV, we look forward to finding the right partner to advance the development of TKM-PLK1 for HCC and maximize the value of this asset for our shareholders."

Trial Design
The Phase I/II TKM-PLK1 HCC clinical study was an open-label, multi-center, study in patients with advanced HCC conducted in the US, Asia, and Canada. The trial was designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of the product. TKM-PLK1 was administered weekly with each four-week cycle consisting of three once-weekly doses followed by a rest week. The study included a total of 43 subjects (12 subjects in the dose escalation arm, followed by 31 subjects in the expansion cohort). The HCC efficacy endpoint of the study was tumor response rate.

About TKM-PLK1
TKM-PLK1 (TKM-080301) is a lipid nanoparticle (LNP) encapsulated small interfering RNA (siRNA) directed against polo-like kinase 1 (PLK1), a protein involved in tumor cell proliferation and a validated oncology target. Inhibition of PLK1 expression prevents the tumor cell from completing cell division, resulting in cell cycle arrest and death of the cancer cell. TKM-PLK1 has been evaluated in clinical trials with patients who have HCC, gastrointestinal neuroendocrine tumors (GI-NET), and adrenocortical carcinoma (ACC).