On February 27, 2020 Harbour BioMed (HBM) reported U.S. Food and Drug Administration (FDA) approval of its Investigational New Drug (IND) application for a Phase 2 clinical trial of HBM9167, its humanized IgG1 monoclonal antibody targeting programmed death-ligand 1 (PD-L1), for the treatment of nasopharyngeal cancer (NPC) (Press release, Harbour BioMed, FEB 27, 2020, View Source [SID1234554899]). Separately, the Agency’s Office of Orphan Products Development granted HBM9167 Orphan Drug Designation (ODD) for the use in treating NPC.

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"Nasopharyngeal cancer is a tumor type for which patients remain in need of effective treatment options," said Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed. "The Orphan Drug Designation for HBM9167 will provide an accelerated development path for HBM9167. In addition, we were also able to work with the FDA to enable a direct entry into a Phase 2 clinical study in patients with metastatic or recurrent disease."

HBM9167 has been evaluated by HBM’s partner Kelun-Biotech in China in studies involving more than 300 subjects to date. These trials include Phase 1 and ongoing Phase 2 trials in multiple cancer types, including NPC and classical Hodgkin’s Lymphoma. Preliminary results from these ongoing trials have shown a tolerable safety profile in patients.

The FDA grants ODD status to drugs intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S. ODD qualifies a drug sponsor for various development incentives under the Orphan Drug Act, such as eligibility for a seven-year period of market exclusivity following regulatory approval, clinical trial assistance and a 50 percent tax credit on the cost of clinical trials conducted in the U.S.

About HBM9167
HBM9167 is a humanized IgG1 monoclonal antibody (mAb) directed against human programmed death-ligand 1 (PD-L1). Through binding with PD-L1, HBM9167 blocks its interaction with programmed cell death protein 1 (PD-1), thereby releasing the PD-L1/PD-1 mediated inhibition on immune response, and subsequently restoring the cytotoxic immune function of T-cells to enhance anti-tumor immunity. Monoclonal antibodies that target PD-1 or PD-L1 can inhibit their binding activity, maintain the function of effector T-cells to prevent cancer cells from escaping the immune surveillance, and thus maintain the body’s immune ability against cancer cells. Harbour BioMed in-licensed HBM9167 from Kelun-Biotech with the right to develop and commercialize it worldwide, excluding Greater China.

On February 27, 2020 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported that an interim analysis of an ongoing Phase 1b study of resiniferatoxin (RTX) administered via epidural route in patients with intractable cancer pain has generated positive data (Press release, Sorrento Therapeutics, FEB 27, 2020, View Source [SID1234554898]). The study is completing enrollment of an additional 25 ug expansion dose cohort. Based on full study results a dose will be selected for RTX to proceed to Phase 3 pivotal trials in patients with advanced cancer pain.

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Safety in the higher dose cohort is expected to be supportive for testing RTX epidural administration in other advanced non-cancer disease related unmet clinical needs (with a choice of starting dose at 15 or 25 ug depending on the indication considered).

Results as planned in the original study (to 15 ug) are being presented at the American Academy of Pain Medicine Annual Meeting on February 27, 2020.

The Phase 1b open-label study was used for dose escalation to assess the safety and preliminary efficacy of a single epidural administration of resiniferatoxin for the treatment of intractable pain due to cancer. Initial expectations for safety and efficacy have been met for the Phase 1b study, though optimal dose selection will follow assessment of the additional dose group in which 25 ug is also being evaluated. Thus far, after Institutional Review Board approval was obtained, and with oversight by an independent data monitoring committee, data is available from 14 subjects with intractable cancer-related pain who received a single epidural injection of RTX from 0.4 to 15 ug.

Safety Outcomes

No dose limiting toxicities or notable adverse events unrelated to progression of underlying disease were encountered for any of the subjects. The most common treatment-related adverse event was transient post-procedural pain: 7 of 14 subjects (50%) reported moderate severity. Two additional treatment-related adverse events of moderate severity were back pain and increase in blood pressure in a patient. All events resolved in less than two days following drug administration.

Efficacy Outcomes

The ongoing trial will follow subjects for at least 84 days. The lower doses of 0.4, 1.0, 2.0, 4.0 ug did not demonstrate notable pain relief, but permitted dose escalation to the next designated dose level based on how well the drug was tolerated.

Three patients had marked pain relief starting shortly after initial administration that were still observed weeks after treatment: 1 of 3 subjects who received 8 ug (a 58-year-old woman with gastrointestinal stromal cancer with severe lower back pain reported a decrease in numerical pain rating scale (NPRS) scores from >6/10 to 2/10), and 2 of 3 subjects who received 15 ug (a 62-year-old man with rectal cancer noted significant improvement in pain, physical strength, mood, and appetite with NPRS scores reduced from 7-8/10 to 3/10; and a 57-year-old man with multiple myeloma and severe pain in his back, hips, and lower extremities subsequently reported mild pain in the target areas after RTX injection). Improvement in pain and mobility within 24 hours of dosing in the three responders at the higher dose levels of RTX suggests the clinical potential of the drug for intractable cancer pain.

Sorrento intends to present the detailed results of the completed study upon completion of the additional expansion cohort later this year. A pivotal Phase 3 trial is being planned using epidural RTX for severe pain states associated with advanced disease.

"We are encouraged by the benefits of using RTX to treat intractable pain in patients with metastatic cancer," said Associate Professor of Anesthesia, Srdjan S. Nedeljkovic, M.D. from the Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital at Harvard Medical School. "Even in patients with high levels of pain, RTX given via an epidural injection has been found to reduce pain intensity without having any long-term adverse safety consequences. The addition of RTX to existing cancer pain therapies represents a positive step forward in improving the care of patients with intractable cancer pain and offers the hope of enhancing the overall quality of life experienced by this population."

For access to the scientific presentation (AAPM poster) please visit
View Source

About Resiniferatoxin (RTX)

A thousand times "hotter" than pure capsaicin (16 Billion Scoville units versus 16M), and with a high affinity for afferent pain nerves, resiniferatoxin binds to TRPV1 receptors and selectively ablates the nerve endings responsible for pain signals experienced by patients1. Delivered peripherally (into the joint space) the transient nerve ending ablation effect can have profound clinical benefits lasting for months to years (as shown in canine studies2).

RTX-001 is a multicenter, open-label dose escalation Phase 1b study to assess the safety and define the maximally tolerated dose of resiniferatoxin administered via the epidural route for the reduction of moderate to severe pain signal intensity associated with advanced cancer. The Phase 1b study is a dose-escalation protocol in which cohorts of patients receive increasing doses of resiniferatoxin until the maximum tolerated dose is achieved. The primary objective of the study is to evaluate the safety of resiniferatoxin and identify the recommended Phase 3 dose. The secondary objective is to assess the preliminary efficacy of resiniferatoxin measured by assessing changes in the intensity of pain using the NPRS score, a widely used proprietary validated pain scale.

RTX is not approved for clinical use by regulatory authorities. Safety and efficacy have not been established.

On February 27, 2020 Boehringer Ingelheim and Trutino Biosciences reported they have entered into a research collaboration and worldwide licensing agreement based on Trutino’s innovative On-Demand-Cytokine (ODC) platform (Press release, Boehringer Ingelheim, FEB 27, 2020, View Source [SID1234554896]). Under the terms of strategic alliance, Boehringer Ingelheim gains access to Trutino’s ODC platform technology for the generation and development of up to three new ODC candidates. This new collaboration combines Boehringer Ingelheim’s long-term strategy to provide first-in-class, breakthrough therapies for cancer patients with Trutino’s unique knowledge and expertise in increasing the safety and efficacy of cytokine therapies.

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"Developing a strong and innovative cytokine therapeutic program as an additional component of our cancer immunology portfolio, demonstrates how we are ‘Taking Cancer On,’ and provides a high potential combination partner for our existing cancer vaccine, oncolytic virus, T cell engager and myeloid-targeting therapeutics portfolio," said Jonathon Sedgwick, Ph.D., Senior Vice President and Global Head, Cancer Immunology & Immune Modulation Research at Boehringer Ingelheim. "We are very pleased to partner with Trutino and harness the potential of their innovative scientific platform to develop treatment breakthroughs that will transform the lives of cancer patients."

Trutino’s ODC platform masks the activity of cytokines until they reach the tumor site and become fully activated, sparing systemic exposure and potentially leading to a higher margin of safety and greater efficacy than conventional cytokine treatments. Trutino will generate the new ODC molecules and carry out preclinical validation, handing over development to Boehringer Ingelheim for late pre-clinical testing through the rest of development.

"We are excited to embark on this partnership with Boehringer Ingelheim, a leader in cancer immunology, to advance cytokine therapeutic options that address the unmet medical needs of patients worldwide," said Phillip Kim, Ph.D., MBA, Founder and CEO of Trutino Biosciences. "Boehringer Ingelheim has a deep commitment to innovative scientific approaches and is a leader in bringing novel cancer therapies to market. This global partnership validates the broad potential of our proprietary ODC platform to create safer and more effective cytokine therapies that can be delivered systemically and activated locally. Together, we can rapidly develop a new generation of cytokine therapies to address critical unmet need in oncology."

Trutino’s clinical potential was initially recognized by Boehringer Ingelheim through its grass roots programs, including the ‘BI Innovation Prize,’ where the ODC platform technology was an early-stage standout in the 2019 program held in San Diego. Launched in 2015, the grass roots programs comprise of ‘BI Office Hours,’ ‘BI Academy’ and the ‘BI Innovation Prize.’ Through Office Hours, Boehringer Ingelheim has provided over 200 early-stage companies in the life-sciences community with mentoring and direct access to relevant expertise and industry perspective from senior leaders within the company. In partnership with BioLabs in Boston, New York and San Diego, Boehringer Ingelheim has awarded numerous entrepreneurs with free lab space through the ‘Golden Ticket’ program. As a company dedicated to improving health and quality of life, these programs give Boehringer Ingelheim the opportunity to lend expertise to the innovation community and offer guidance around the science to help enable ideas to deliver the next breakthroughs.

The partnership with Trutino will strengthen Boehringer Ingelheim’s next generation immune oncology portfolio, which combines cancer vaccines, oncolytic viruses, T Cell engagers and myeloid targeting platforms with the aim of making "cold" tumors that are invisible to the immune system "hot" to rally the immune system against the tumor. Under the terms of the agreement, Boehringer Ingelheim will provide an upfront payment, near-term pre-clinical milestone payments and clinical, regulatory and commercial milestone payments, including royalties on future product sales.

On February 26, 2020 Pfenex Inc. (NYSE American: PFNX) reported that it will report its financial results for the fourth quarter and year ended December 31, 2019, after the market close on Wednesday, March 11, 2020 (Press release, Pfenex, FEB 26, 2020, View Source [SID1234554895]). Pfenex will host a conference call and webcast to discuss its financial results and provide a company update that day at 1:30 PM Pacific Time (4:30 PM Eastern Time).

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Conference Call & Webcast
Wednesday, March 11th @ 1:30 PM Pacific Time (4:30 PM Eastern Time)
Domestic: 866-376-8058
International: 412-542-4131
Webcast: View Source

Replays available through March 18th:
Domestic: 877-344-7529
International: 412-317-0088
Replay Access Code: 10139830

On February 27, 2020 MapKure, LLC, a clinical-stage company developing precision medicines for patients with life-threatening diseases, together with BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160) and SpringWorks Therapeutics, Inc. (NASDAQ: SWTX), who are joint owners of MapKure, reported that the first patient has been dosed in Australia in a Phase 1 clinical trial to evaluate BGB-3245, an investigational, next-generation B-RAF inhibitor, in patients with advanced or refractory solid tumors (Press release, MapKure, FEB 27, 2020, View Source [SID1234554894]). The companies also announced that the U.S. Food and Drug Administration (FDA) has allowed the Investigational New Drug (IND) application submitted for BGB-3245 to proceed, which will enable study expansion to U.S. sites.

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B-RAF gene mutations and fusions have been shown to play a key role in the development of certain cancers. BGB-3245 is designed to inhibit both monomeric and dimeric forms of activating B-RAF mutations including V600 and non-V600 mutations, and RAF fusions, and has shown potent preclinical activity against a range of B-RAF gene alterations, including those for which there are no approved targeted therapies and those associated with resistance to currently approved therapies.

"Preclinical data suggest that BGB-3245 could potentially address a range of B-RAF driven tumors, which represent a significant need for patients who currently lack targeted therapeutic options, as well as patients who have developed resistance to first generation B-RAF inhibitors," said Neal Rosen, M.D., Ph.D., the Enid A. Haupt Chair in Medical Oncology at Memorial Sloan-Kettering Cancer Center and Chair of the MapKure Scientific Advisory Board. "If our hypothesis is correct, we believe that BGB-3245 could have meaningful, single agent antitumor activity in B-RAF-altered cancers through its ability to address key primary and resistance gene alterations that are currently unaddressed by approved therapies."

The Phase 1 clinical trial is a first-in-human, open-label, dose escalation and expansion study to investigate the safety, pharmacokinetics (PK) and antitumor activity of BGB-3245 in adult patients with solid tumors, including those harboring specific B-RAF driver mutations and fusions that are likely to respond to a RAF dimer inhibitor, as well as in certain adult patients who have developed resistance to first-generation B-RAF V600 inhibitors. The trial is designed to define the dose and assess the tolerability of BGB-3245 and will capture early antitumor activity signals to allow for potential cohort expansion.

In addition, MapKure has completed the formation of its Scientific Advisory Board (SAB), comprised of renowned leaders in MAPK pathway biology and targeted oncology clinical development. The SAB will continue to collaborate with MapKure’s joint steering committee, consisting of representatives from BeiGene and SpringWorks, to support the advancement of BGB-3245. The composition of the SAB is as follows:

Neal Rosen, M.D., Ph.D., the Enid A. Haupt Chair in Medical Oncology at Memorial Sloan-Kettering Cancer Center. Dr. Rosen is the founding member and Chair of the MapKure SAB.
Antoni Ribas, M.D., Professor of Medicine, Professor of Surgery, and Professor of Molecular and Medical Pharmacology at the University of California Los Angeles.
Kevin Koch, Ph.D., President and CEO of Edgewise Therapeutics; formerly Founder, President, and Chief Scientific Officer of Array BioPharma.
Zhan Yao, Ph.D., Assistant Research Professor, Molecular Pharmacology Program, Memorial Sloan-Kettering Cancer Center.
Dejan Juric, M.D., Program Director, Investigational Cancer Therapeutics Program and Attending Physician in Medical Oncology, Massachusetts General Hospital.
About the Phase 1 Trial

The Phase 1 trial (NCT04249843) of BGB-3245 is an open-label, dose-escalation trial of BGB-3245 in adult patients with advanced or refractory solid tumors, including those with B-RAF driver mutations and fusions that are likely to respond to a RAF dimer inhibitor. The study will enroll patients who have experienced disease progression during or after at least one prior line of systemic anticancer therapy or for which treatment is not tolerated or acceptable to the participants.

The trial is designed in two parts: the Phase 1a portion will consist of a dose-escalation and dose-finding component to establish the maximum tolerated dose and/or the recommended Phase 2 dose and to evaluate the pharmacokinetics of BGB-3245 in patients with MAPK pathway aberrations. The Phase 1b portion will consist of one or more expansion cohorts to further evaluate the pharmacokinetics, safety, and tolerability of BGB-3245 at the recommended Phase 2 dose and to assess the preliminary antitumor activity of the compound in patients with select tumor types and B-RAF status (B-RAF point mutations and gene fusions).

About BGB-3245

BGB-3245 is an investigational, oral, selective small molecule inhibitor of monomer and dimer forms of activating B-RAF mutations including V600 B-RAF mutations, non-V600 B-RAF mutations, and RAF fusions. These mutations and fusions have been identified in a number of solid tumors to be drivers of cancer growth, including in non-small cell lung cancer, colorectal cancer, thyroid cancer, and brain tumors. Preclinical data have demonstrated that BGB-3245 has activity in patient-derived xenografts driven by B-RAF fusions and non-V600 mutations for which approved B-RAF inhibitors are ineffective. In addition, BGB-3245’s preclinical activity in cancer models driven by V600 B-RAF mutations has suggested that it could provide an additional therapeutic option for patients with the potential to reduce dimer-driven resistance.

In addition to its intended use as a monotherapy in several genetically defined solid tumor types, BGB-3245 also has the potential to be used in rational combination therapies in the future.