On July 20, 2020 Rhythm Pharmaceuticals, Inc. (Nasdaq:RYTM), a late-stage biopharmaceutical company aimed at developing and commercializing therapies for the treatment of rare genetic disorders of obesity, reported that David Meeker, M.D., the Chairman of Rhythm’s Board of Directors, has been appointed as the President and Chief Executive Officer (CEO) of the company, effective immediately (Press release, Rhythm Pharmaceuticals, JUL 20, 2020, View Source [SID1234562167]). Dr. Meeker succeeds Hunter Smith, the Company’s Interim President and CEO and Chief Financial Officer (CFO), who will continue in his role as CFO.

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"I am delighted to announce David’s appointment as Rhythm’s new CEO," said Hunter Smith, CFO of Rhythm. "Since he joined our Board in 2015, David has played a key role in shaping the clinical and commercial strategy for setmelanotide and in fostering our collaborative and patient-focused culture. As we continue to work toward the first potential approval of setmelanotide in pro-opiomelanocortin (POMC) and leptin receptor (LEPR) deficiency obesities later this year, David’s extensive experience leading commercial organizations and managing the launches of new medicines for rare genetic diseases, coupled with his proven ability to build strong relationships with patient and clinician communities, will be invaluable. The Rhythm team is energized by the opportunity to work more closely with David in an effort to deliver setmelanotide and potentially transform the care of people living with rare genetic disorders of obesity."

"Rhythm is an exciting company that I have long admired, both for its scientifically-rigorous approach to drug development and its commitment to patients with rare genetic disorders of obesity," said David Meeker, M.D. "With setmelanotide, we have the opportunity to bring one of the first meaningful therapeutic candidates to a segment of that community in dire need. Moreover, we hope our efforts will create visibility for rare genetic disorders of obesity, enabling better care for the people affected and catalyzing ongoing research efforts globally. The current management team has done a great job leading the organization through the transition and I am honored to take the CEO role."

Dr. Meeker has served as Chairman of Rhythm Pharmaceuticals since April 2017 and as a member of the Board since November 2015. Most recently, he served as President and CEO of KSQ Therapeutics. Previously, Dr. Meeker was the Executive Vice President and Head of Sanofi Genzyme, the specialty-care global business unit of Sanofi that focuses on rare diseases, multiple sclerosis, oncology and immunology. Dr. Meeker joined Genzyme in 1994 as Medical Director and, over the course of his tenure, served the company as Vice President of Medical Affairs, Chief Operating Officer, and Chief Executive Officer. He led Genzyme’s commercial organization and global market access functions and managed the launch of several treatments for rare genetic diseases, including Aldurazyme, Fabrazyme and Myozyme. Prior to his tenure with Genzyme, Dr. Meeker was Director of the Pulmonary Critical Care Fellowship at the Cleveland Clinic and an Assistant Professor of Medicine at Ohio State University. Dr. Meeker earned his M.D. from the University of Vermont Medical School and completed the advanced management program at Harvard Business School.

On July 20, 2020 Bioniz Therapeutics, Inc., a clinical stage biopharmaceutical company developing first-in-class peptide therapeutics that selectively and simultaneously inhibit multiple cytokines to treat immuno-inflammatory diseases and cancers, reported encouraging interim clinical data from its Phase 1/2 open-label clinical study of its lead product candidate BNZ-1 in patients with refractory Cutaneous T-Cell Lymphoma (rCTCL) (Press release, Bioniz Therapeutics, JUL 20, 2020, View Source [SID1234562144]). BNZ-1 is a multi-cytokine inhibitor targeting interleukin (IL)-2, IL-9, and IL-15, that has been successfully studied in two phase 1 studies in healthy volunteers where it demonstrated a favorable safety profile, dose proportionality and exposure-dependent pharmacodynamic activity .

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This study followed a phase 1/2, multi-center, open-label, dose-escalation clinical study of BNZ-1 and was designed to assess its safety and activity as a single systemic agent in rCTCL patients that have failed standard of care and other available treatment options. The study was designed to recruit a total of 15 patients across 4 doses of 0.5, 1, 2, and 4 mg/kg for intravenous weekly dosing. The primary endpoint was overall safety after 4 weeks of treatment. There was a 3-month treatment extension to further evaluate safety and clinical response. Long term extension was available for patients who benefited from BNZ-1 treatment.

Whereas efficacy was observed in all cohorts, the 2 mg/kg cohort was expanded to 19 patients based on a favorable initial clinical response. Overall, BNZ-1 was well tolerated with no dose-limiting toxicities. On average, these rCTCL patients had failed 7 prior skin-directed and systemic therapies. The 2 mg/kg cohort showed signs of clinical improvement with BNZ-1 treatment, as follows:

Over 80% of subjects showed some improvement in tumor burden as assessed by the modified severity weighted assessment tool (mSWAT) score in the absence of any concomitant therapy
About half achieved a partial response (at least a 50% reduction from baseline) in mSWAT score
5% of subjects achieved a complete response
For subjects achieving a partial or complete response, the mean duration of response was 277 days (9.2 months) at the time of the data cut off for this interim analysis
Dr. Christiane Querfeld, Director of the Cutaneous Lymphoma Program at the City of Hope, who was the principal investigator of this study, stated "I am pleased with the interim results of the BNZ-1 trial in a highly refractory patient population. Based on this interim analysis, BNZ-1 appears to be safe and well tolerated in CTCL patients. In this trial, BNZ-1 has shown efficacy in heavily pretreated and/or advanced stage patients who have failed standard of care and investigational drugs available to them. As a physician, I look forward to the continued development of BNZ-1 and hope to eventually have this drug in my practice to treat and manage my CTCL patients."

"Together with our investigators, we are excited to see the potential clinical benefit of BNZ-1 in highly refractory CTCL patients," said Dr. Nazli Azimi, Founder, President and Chief Executive Officer of Bioniz Therapeutics. "We are eager to further advance the clinical development of BNZ-1 towards approval in CTCL and to evaluate its potential clinical efficacy in other dermatological diseases such as alopecia areata and vitiligo." She added "these data provide additional validation of our platform technology and our approach for multi-cytokine inhibition".

Bioniz expects this study to conclude in early Q3 of this year and will submit a request for an end of phase 2 meeting in Q4. Based on the outcome of this meeting, Bioniz anticipates starting phase 3 in 1H 2021.

About T-Cell Leukemia and Lymphoma
T-cell leukemia and lymphoma include a group of rare and often aggressive diseases, including CTCL with limited treatment options and a poor prognosis. Bioniz’ product candidate BNZ-1 is a selective inhibitor of cytokines IL-2, IL-9, and IL-15, which are potent T-cell growth factors and key disease drivers in this T-cell malignancy.

About BNZ-1
The Company’s lead development candidate, BNZ-1, is a PEGylated peptide that functions as a selective and simultaneous inhibitor of cytokines IL-2, IL-9, and IL-15. BNZ-1 is currently under investigation in a phase 1/2 clinical trial for refractory Cutaneous T-Cell Lymphoma (rCTCL) and Large Granular Lymphocyte (LGL) Leukemia (www.clinicaltrials.gov identifier: NCT03239392).

On July 20, 2020 JW Therapeutics, a clinical stage biopharmaceutical company focused on developing, manufacturing and commercializing cell therapies for patients in China, reported the acquisition of Syracuse Biopharma (Hong Kong) Limited, which includes the license for Eureka Therapeutics’ ARTEMIS antibody TCR and solid tumor technology for exclusive use in China and the ASEAN countries (Press release, JW Therapeutics, JUL 20, 2020, View Source [SID1234562140]).

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Terms of the transaction were not disclosed. Dr. Cheng Liu, Founder and President of Eureka Therapeutics, will join the Board of Directors of JW Therapeutics, and Victor Shum, Chief Business Officer and General Counsel of Eureka, will join as a Board Observer.

"We are excited to announce our acquisition of Syracuse, to expand our clinical development into solid tumor cancers," said Dr. James Li, Co-Founder and CEO of JW Therapeutics. "Syracuse and Eureka have developed an elegant approach to treating solid tumors with their TCR-mimic and ARTEMIS technologies. We’re looking forward to working with the team to bring the next generation of T cell immunotherapies to patients."

"We are excited that JW Therapeutics, the industry leader in cell immunotherapies in China, has recognized the value of our ARTEMIS platform, and shares our passion and urgency for developing innovative immunotherapies for patients with cancer," said Dr. Cheng Liu, Founder and CEO, Eureka Therapeutics. "With JW’s expertise, network and support, we hope to accelerate development of our T cell therapies against solid tumors. The incidence rate of HCC is very high in China, and JW is well positioned to use their broad expertise to develop these therapies and bring them to patients faster."

On July 20, 2020 NeoImmuneTech, Inc., a clinical-stage T cell-focused biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application for the combination of NeoImmuneTech’s NT-I7 (efineptakin alfa), a novel long-acting human interleukin-7 (IL-7), and Bristol Myers Squibb’s Opdivo (nivolumab), a PD-1 blocking antibody, for the treatment of patients with advanced or metastatic gastric, gastro-esophageal junction (GEJ), or esophageal adenocarcinoma (EAC) (Press release, NeoImmuneTech, JUL 20, 2020, View Source [SID1234562139]). This IND clearance allows NeoImmuneTech (NIT) to initiate a randomized Phase 2 study comparing NT-I7 + nivolumab versus nivolumab to evaluate preliminary anti-tumor activity and to establish safety and tolerability of the combination in these patients.

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"This new clearance marks another key milestone in our rapidly expanding clinical program of NT-I7, our unique T cell amplifier. NT-I7’s excellent safety profile and function as an immune enhancer can potentially broaden and deepen the anti-tumor response in combination with checkpoint inhibitors such as Opdivo," said NgocDiep Le, MD, PhD, Executive Vice President and Chief Medical Officer of NIT. "At present, there are only limited treatment options available for patients with advanced gastric cancer after failure of two prior treatments. We look forward to initiating the study as soon as possible to address high unmet medical need in these patient populations."

The results of this Phase 2, proof-of-principle study will be used to further clinical development of this combination in selected clinical settings and tumor types.

"As a company, we work tirelessly to expand our development of NT-I7, both as a single agent and in combination with current immunotherapeutics where it has the potential to further expand the patient populations that could benefit from such therapies," said Se Hwan Yang, PhD, President and Chief Executive Officer of NIT. "NT-I7 is uniquely positioned to support such immunotherapy treatments, as it may be able to increase the number and diversity of T cells that are activated by checkpoint inhibition to fight cancer more effectively. We hope that our dedication and effort can bring NT-I7 to patients in need in the foreseeable future."

Opdivo is a registered trademark of Bristol Myers Squibb.

About NT-I7

NT-I7 (efineptakin alfa) is the only clinical-stage long-acting human IL-7, and is being developed for oncologic and immunologic indications, in which T-cell amplification and increased functionality may provide clinical benefit. IL-7 is a fundamental cytokine for naïve and memory T-cell development and for sustaining immune response to chronic antigens (as in cancer) or foreign antigens (as in infectious diseases). NT-I7 exhibits favorable PK/PD and safety profiles, making it an ideal combination partner. NT-I7 is being studied in multiple clinical trials in solid tumors and as a vaccine adjuvant. Studies are being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications.

On July 20, 2020 Exelixis, Inc. (NASDAQ: EXEL) reported the initiation of CONTACT-03, a global phase 3 pivotal trial of cabozantinib (CABOMETYX) in combination with atezolizumab (TECENTRIQ) in patients with inoperable, locally advanced or metastatic renal cell carcinoma (RCC) who progressed during or following treatment with an immune checkpoint inhibitor as the immediate preceding therapy (Press release, Exelixis, JUL 20, 2020, View Source [SID1234562138]). CONTACT-03 is part of a clinical trial collaboration between Exelixis and Roche that includes two additional phase 3 pivotal trials – CONTACT-01 in patients with metastatic non-small cell lung cancer (NSCLC) who have been previously treated with an immune checkpoint inhibitor and platinum-containing chemotherapy and CONTACT-02 in patients with metastatic castration-resistant prostate cancer (CRPC) who have been previously treated with one novel hormonal therapy – both initiated in June 2020.

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"The treatment landscape for metastatic kidney cancer is rapidly evolving as the use of immune checkpoint inhibitor-based regimens move to earlier lines of therapy," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "More data are needed to better understand the sequential use of treatments for this patient community, and we look forward to learning more about the potential role of the combination of cabozantinib and atezolizumab following checkpoint inhibitor therapy in this pivotal trial with our partner Roche."

CONTACT-03 is a global, multicenter, randomized, phase 3, open-label study that aims to enroll approximately 500 patients. Patients will be randomized 1:1 to the experimental arm of cabozantinib in combination with atezolizumab or the control arm of cabozantinib alone. The co-primary endpoints of the trial are progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 as assessed by independent review and overall survival. Secondary endpoints include progression-free survival, objective response rate and duration of response as assessed by the investigators. The CONTACT-03 trial is sponsored by Roche and co-funded by Exelixis.

The design of CONTACT-03 was informed by the ongoing COSMIC-021 trial — a phase 1b study of cabozantinib in combination with atezolizumab in multiple advanced solid tumors including RCC, NSCLC and CRPC. More information about CONTACT-03 is available at ClinicalTrials.gov (NCT04338269).

About RCC

The American Cancer Society’s 2020 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common type of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12%.2 Approximately 32,000 patients in the U.S. and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2020.3

About 70% of RCC cases are known as "clear cell" carcinomas, based on histology.4 The majority of clear cell RCC tumors have below-normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.5,6 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.7,8,9,10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.6,7

About CABOMETYX (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with HCC who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide.

CABOMETYX in combination with atezolizumab is not indicated for metastatic renal cell carcinoma.

About Exelixis’ Collaboration with Ipsen
On February 29, 2016, Exelixis and Ipsen jointly announced an exclusive collaboration agreement for the further development and commercialization of cabozantinib outside of the United States, Canada and Japan. On December 21, 2016, this agreement was amended to include commercialization rights for Ipsen in Canada. Under the parties’ collaboration agreement, if Ipsen opts to participate in funding this phase 3 trial, or future studies, it will have access to the respective study results to support potential future regulatory submissions in their territory.

About Exelixis’ Collaboration with Takeda
On January 30, 2017, Exelixis and Takeda jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications in Japan. Under the parties’ collaboration agreement, if Takeda opts to participate in funding this phase 3 trial, or future studies, it will have access to the respective study results to support potential future regulatory submissions in their territory.

Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

Important Safety Information

Warnings and Precautions

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Proteinuria: Proteinuria occurred in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, and vomiting.

Drug Interactions

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.