On April 7, 2022 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, and MediSix Therapeutics, a cell therapy company creating novel therapeutics to target T-cell leukemia and lymphoma, reported a collaboration to discover novel antibodies against five undisclosed targets (Press release, Twist Bioscience, APR 7, 2022, View Source [SID1234611622]).

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Under the terms of the collaboration, Twist will leverage its proprietary Library of Libraries to discover five novel antibodies directed against MediSix’s targets. MediSix will use its unique platform technologies to develop novel CAR T-cell therapies targeting malignancies and autoimmune diseases without any CAR T-cell fractricide. Twist will receive an upfront payment and will be eligible to receive success-based clinical and regulatory milestone payments, as well as royalties on product sales.

"We believe Twist’s exceptional antibody discovery and optimization platform and extensive libraries, coupled with the company’s ability to move quickly and efficiently, will support our efforts to develop effective immune cell therapies that specifically modulate relevant molecules and combat T-cell malignancies and autoimmune diseases," said Andrew Bruce, CEO of MediSix Therapeutics. "We look forward to continued work with Twist as we build our pipeline."

"We look forward to collaborating with MediSix to overcome existing challenges of using cell therapy approaches to treat T-cell malignancies, often because of a lack of antigen targets specific to the cancer. Pairing MediSix’s novel targets with our ability to discover and optimize antibodies to efficiently target these devastating cancers has the potential to add an important and needed therapeutic option for patients," said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. "In addition, with MediSix’s locations in Boston, U.S. and Singapore, this agreement deepens our global footprint and presence in the Asia Pacific region, where certain types of T-cell cancers are more prevalent."

On April 7, 2022 Sequence Bio, a Newfoundland and Labrador-based discovery biology company, reported that it has entered into a collaboration agreement with Danish dermatology specialists LEO Pharma, for use of Sequence Bio’s proprietary discovery platform to identify novel dermatologic drug targets (Press release, Leo, APR 7, 2022, View Source [SID1234611620]). Under the terms of the three year agreement, Sequence Bio will perform multi-omic analyses of samples from powered discovery cohorts across multiple dermatologic indications. LEO Pharma will leverage insights generated under this collaboration to build robust evidence in support of new potential approaches that significantly impact dermatologic conditions.

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"We are delighted to enter this collaboration agreement with Sequence Bio to further accelerate LEO Pharma’s ambition to identify novel dermatologic drug targets," said Thorsten Thormann, Vice President of Research & Early Development in LEO Pharma. "LEO Pharma is relentlessly committed to making pioneering advances in dermatology research and bringing new treatments to patients faster."

"We are excited to work with LEO Pharma on their mission to positively impact millions of lives through medical dermatology," said Dr. Richard Leach, Chief Strategy Officer of Sequence Bio. "This collaboration aligns with our strategic priorities to expand the potential of our discovery platform to power life-changing medicines in areas of unmet medical need across the globe."

On April 7, 2022 Oxford BioTherapeutics (OBT), a clinical stage oncology company with a pipeline of immuno-oncology and Antibody Drug Conjugate (ADC)-based therapies, reported a forthcoming presentation featuring preliminary clinical data from its ongoing Expansion Phase I Trial (NCT04064359) of its experimental CD205-directed ADC, OBT076, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, taking place 8th – 13th April in New Orleans, US (Press release, Oxford BioTherapeutics, APR 7, 2022, View Source [SID1234611619]).

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The presentation highlights are below:

Near complete responses in two chemo-refractory advanced cancer patients with low PD-L1 expression after 2-5 cycles of OBT076 and 1-2 cycles of a CPI indicate preliminary signs of clinical activity, and
Translational work on patients receiving OBT076, followed by an immune CPI, whose immuno- blood profiling revealed a potential novel immuno-oncology mechanism for immune system reactivation and tumor shrinkage.
"We are pleased to share these data showing promising preliminary signs of clinical activity and a favorable tolerability profile for our experimental CD205-directed ADC, OBT076, in patients with advanced and chemo-refractory cancers," said Christian Rohlff, PhD, Chief Executive Officer (CEO) of Oxford BioTherapeutics. "The results support our excitement around OBT076 as a therapeutic capable of harnessing the immune system to treat patients with advanced, difficult to treat cancers both as monotherapy and in combination with a CPI. Our preliminary data suggest that depletion of CD205+ immuno-suppressive cells and subsequent T-cell activation after OBT076 treatment followed by a single cycle of a CPI coincides with the rapid resolution of the primary tumor, as well as metastases in a chemo-refractory advanced gastric cancer patient."

Summary of the Data to Be Presented at AACR (Free AACR Whitepaper)

The objective of the translational work emerging from the ongoing Phase I OBT076 trial (NCT04064359), presented at AACR (Free AACR Whitepaper), is to evaluate the antitumor activity of OBT076, at a lower test dose of 2.0-2.5 mg/kg, in combination with a CPI in chemo-refractory solid tumor patients.

As of the data cut-off (January 31, 2022), 2 patients with advanced solid tumors with at least 1 metastatic site had been treated with the combination. Patient 1 received OBT076 for 5 cycles; the first cycle at 2.5 mg/kg and subsequent cycles at 2.0 mg/kg, followed by 1 cycle of a CPI at 200 mg approximately 2 weeks later. Clinical response was evaluated and immunological markers (CD45, CD205, CD4, CD8, and PD1) in peripheral blood cells were quantified using flow cytometry.

Patient 1 had a diagnosis of chemo-refractory advanced gastric cancer with 60% CD205 expression in the primary tumor and had previously undergone 2 lines of conventional chemotherapy treatment. After 3 OBT076 cycles at 2.0 mg/kg, there was a ~40% shrinkage in the primary gastric tumor size and resolution of ascites and lymph node metastases.

Following 2 further cycles of OBT076 and 1 cycle of CPI, complete response was achieved for the primary tumor. Flow cytometry showed simultaneously occurring increases in PD1+ T-cells, T-cell induction, and decreases in immuno-suppressive CD4+ CD205+ and CD8+ CD205+ cells; coinciding with rapid resolution of the primary tumor, lymph node metastases and ascites.

Similar findings were reported for Patient 2 after 2 cycles with OBT076 followed by CPI. Both Patients 1 and 2 had near complete response after treatment with OBT076 followed by 1-2 cycles with CPI despite having low PD-L1 expression.

"These findings suggest that OBT076 may activate the patient’s immune response against the tumor through a potentially novel mechanism: drug-induced depletion of CD8+ CD205+ immuno-suppressive cells and subsequent T- cell activation," said Rahim Fandi, MD, PhD, Chief Medical Officer (CMO) of Oxford BioTherapeutics. "The treatment of patients who are resistant to therapy with CPIs is challenging. These data give us hope that OBT076 could achieve favorable clinical outcomes in such patients when used in combination with immune CPIs. Based on these encouraging results, we are advancing OBT076 into the next stage of clinical development as both a single agent and in combination with a CPI, for the treatment of multiple solid tumor indications, with the goal of improving outcomes for patients with difficult-to-treat cancers."

The e-poster and abstract will be accessible on the AACR (Free AACR Whitepaper) conference website. The abstract and presentation details are as follows:

Title: Potential Novel Immuno-oncology Mechanism revealed during Translational Phase I Immuno- blood Profiling of Experimental ADC medicine OBT076 in A Gastric Cancer Patient.

Session: Immune Response to Therapies / Immune Monitoring and Clinical Correlates

Date: 11th April 2022 13:30:00 PM

Location: Poster Section 31
Poster #: 5497

Authors: Christian Rohlff et al.

OBT076 Further Clinical Development Plans

Based on these preliminary results, OBT plans to advance OBT076 as a monotherapy as well as in combination in trials in both checkpoint-naïve and resistant patients. These Phase 1b trials will assess the safety of OBT076 in combination with CPI in patients with solid tumors, and as a monotherapy in patients with solid tumors. Subsequent disease-specific Phase 2a trials are planned in patients with non-small cell lung cancer, ovarian cancer and gastric cancer. OBT is also planning for later-stage trials of OBT076, including in combination with CPI.

On April 7, 2022 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the United States Food and Drug Administration (FDA) has granted Orphan-Drug Designation (ODD) for HANSIZHUANG (serplulimab) for the treatment of small cell lung cancer (SCLC). This is the first such designation granted to HANSIZHUANG (Press release, Shanghai Henlius Biotech, APR 7, 2022, View Source [SID1234611618]). The ODD granted by the FDA is beneficial for the continuous development of HANSIZHUANG and the enjoyment of certain policy support in terms of registration and commercialization in the United States. The company plans to file its NDA in China and MAA in the EU in 2022, making HANSIZHUANG potentially to be the world’s first PD-1 inhibitor for the first-line treatment of SCLC.

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Orphan drugs refer to pharmaceutical products developed for the prevention, diagnosis, and treatment of rare diseases or conditions affecting fewer than 200,000 people in the U.S. at the time of designation and to offer certain policy support, including but not limited to: 1) tax credits for clinical trial costs; 2) waiver of application fees for new drugs; and 3) seven years of market exclusivity without being affected by patent.

According to GLOBOCAN 2020, lung cancer (LC) is the second most common cancer around the world. There were 2.2 million new LC cases and 1.8 million new deaths in 2020 worldwide, and LC is the leading cause of cancer deaths[1]. SCLC accounts for 15%–20% of all cases and is the most aggressive type of LC. It is classified into two stages: limited stage (LS-SCLC) and extended stage (ES-SCLC), with both exhibiting high malignancy, strong invasiveness, early metastasis, fast disease progression, and a poor prognosis. The advent of immune checkpoint inhibitors has been proved to bring hope to patients with ES-SCLC but fraught with challenges. In recent years, a number of PD-1 mAbs have failed in the area. On the other hand, the standard treatment regimens for LS-SCLC are surgery, chemotherapy and concurrent radiotherapy. Traditional chemotherapeutic drugs did not exhibit significant progress in patients with LS-SCLC, and most patients tend to develop drug resistance or rapid relapse[2-4].

Based on the unmet clinical needs, Henlius promotes a series of immunotherapy studies in the field of SCLC, with the goal of providing more effective treatment approaches for patients. Henlius has undertaken multiple trials to investigate therapy options for both LS-SCLC and ES-SCLC, including the global multi-centre phase 3 study of HANSIZHUANG for the first-line treatment of ES-SCLC (ASTRUM-005) and the investigational new drug application (IND) of international multi-centre phase 3 studies of HANSIZHUANG (serplulimab) approval from the National Medical Products Administration (NMPA). In detail, ASTRUM-005 is a randomised, double-blind, international, multi-centre, phase 3 clinical study aimed to compare the efficacy and safety of HANSIZHUANG with placebo when combined with chemotherapy (carboplatin-etoposide) in previously untreated patients with SCLC. This study has set up about 128 sites in China, Turkey, Poland, Georgia, etc. and 585 subjects were enrolled, among whom 31.5% were Caucasian. In Dec 2021, ASTRUM-005 has met the primary study endpoint of the overall survival (OS), reducing the risk of death by 38% of the overall population (41% in the Asian subgroup). Based on the excellent readouts, the company intends to file NDA for the indication shortly.

In the future, Henlius will continue to emphasize unmet clinical needs and actively promote the combination immunotherapy of serplulimab and international regulatory registration to benefit more patients around the world.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. It is approved by the NMPA for the treatment of MSI-H solid tumors in March 2022. Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company and innovative therapies. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 9 clinical trials on immuno-oncology combination therapies of HANSIZHUANG worldwide in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. Up to date, the company has enrolled more than 2,800 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of Caucasians is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDA of the treatment for squamous non-small cell lung cancer (sqNSCLC) has been accepted by the NMPA and is expected to be approved in 2022. Furthermore, the global multi-center phase 3 clinical study of HANSIZHUANG in combination with chemotherapy in previously untreated extensive small-cell lung cancer (ES-SCLC) met the primary endpoint of overall survival (OS) with remarkable readouts and its NDA in China and MAA in the EU are expected to be filed in 2022, making this product potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC.

On April 7, 2022 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T cell therapies for the treatment of hematologic malignancies and solid tumors, reported that Dr. Raffaele Baffa ("Dr. Baffa") has been appointed as the Chief Medical Officer ("CMO") of the Company, responsible for overseeing the global clinical development strategies and operations for the Company’s innovative pipeline product candidates (Press release, Carsgen Therapeutics, APR 7, 2022, View Source [SID1234611617]). Dr. Baffa will report to Dr. Zonghai Li, Founder, Chairman of the Board, CEO, CSO of CARsgen Therapeutics Holdings Limited.

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Dr. Baffa has rich experiences in pharmaceutical industry and research institutes, taking various leadership positions in multi-national corporations and biotech companies. Prior to joining CARsgen, Dr. Baffa served as Chief Medical Officer and Executive Vice President of Research & Development at Ziopharm Oncology (NASDAQ: ZIOP), which was rebranded to Alaunos in January 2022. (NASDAQ: TCRT). Prior to Ziopharm Oncology, Dr. Baffa was Head of Research & Development and Chief Medical Officer in Medisix Therapeutics, a company focused on developing novel immune cell therapies. Dr. Baffa was the Vice President, Therapeutic Area Head of Oncology, Global Clinical Development of Shire Pharmaceuticals, and following the acquisition of the oncology division by Servier Pharmaceuticals, Dr. Baffa served as the Chief Medical Officier of Servier Pharmaceuticals. Dr. Baffa has also held leadership positions at well-known pharmaceutical companies, such as Pfizer and Sanofi.

Dr. Baffa earned an M.D. from University of Padova, School of Medicine and a Ph.D. in biology and molecular pathology from University of Parma in Italy.

Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics Holdings Limited, said, "We warmly welcome Dr. Baffa to join CARsgen. Dr. Baffa is a medical professional and industry veteran with extensive experiences in clinical development and translational sciences in the field of oncology and cellular immunotherapy. Dr. Baffa brings a wealth of clinical, medical, and leadership experiences from multinational corporations and biotechnology companies. Dr. Baffa joins us at an exciting time as the clinical trials for both CT053 and CT041 are progressing in North America and being explored in other territories. Dr. Baffa’s joining will further accelerate the global clinical development of our innovative product candidates."

Dr. Raffaele Baffa, Chief Medical Officer of CARsgen Therapeutics Holdings Limited, said, "I am very excited to join CARsgen. As one of the leading companies in cell therapies globally, CARsgen has developed a rich and differentiated product pipeline and a suite of exciting technology platforms such as THANK-uCAR for allogeneic CAR T and LADAR for precise targeting. CARsgen has also shown big ambitions with continuous investment for the global market, such as the establishment of the manufacturing facility in the United States. I look forward to working closely with colleagues in CARsgen and external partners to accelerate CARsgen’s global clinical development and bring more innovative products to cancer patients."