On April 7, 2022 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) and Werewolf Therapeutics, Inc. (Nasdaq: HOWL) reported that the companies have entered into a licensing agreement under which Jazz has acquired exclusive global development and commercialization rights to Werewolf’s investigational WTX-613, a differentiated, conditionally-activated interferon alpha (IFNα) INDUKINE molecule (Press release, Jazz Pharmaceuticals, APR 7, 2022, View Source [SID1234611640]).

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"We believe WTX-613 has the potential to minimize the toxicity associated with systemic IFNα therapy, preferentially delivering IFNα to tumors, and thereby expanding its clinical utility in treating cancer. We are excited about the potential of WTX-613 based on compelling proof-of-concept data, recently presented at ASH (Free ASH Whitepaper), where a WTX-613 surrogate molecule demonstrated anti-tumor activity in preclinical models," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "This transaction underscores our commitment to enhancing our pipeline to deliver novel oncology therapies to patients, and also provides us with an opportunity to expand into immuno-oncology. We will continue to identify and advance promising treatments and novel combinations as we aim to deliver at least five additional novel therapies to patients by the end of the decade as part of our Vision 2025."

WTX-613 is currently in preclinical development. Jazz expects to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for WTX-613 in 2023.

"We are thrilled to join forces with Jazz to advance WTX-613 on behalf of patients," said Daniel J. Hicklin, Ph.D., president and chief executive officer of Werewolf. "This partnership comes at an exciting time for Werewolf and enables WTX-613 to rapidly move toward the clinic, while we continue to advance our lead programs, WTX-124 and WTX-330, through expected IND filings this year."

WTX-613 is an engineered IFN⍺2b cytokine pro-drug that is activated specifically within the tumor microenvironment where it can stimulate IFNα receptors on cancer-fighting immune effector cells. The aim of WTX-613 is to minimize the severe toxicities that have been observed with systemically active recombinant IFNα therapy and maximize clinical benefit when administered as monotherapy or in combination with other agents. Type 1 interferon signal transduction by IFNα agonism is a clinically validated mechanism of action, and IFNα has been shown to work synergistically in combination with other proven therapies including immune checkpoint inhibitors, targeted therapies and chemotherapy. This allows for potential application of WTX-613 across a wide range of cancer types, combination regimens and lines of therapy. WTX-613 was created leveraging Werewolf’s proprietary PREDATOR protein engineering technology, which integrates specialized protein design elements to enhance activity, stability and tumor selectivity within a single molecule, called INDUKINE molecules.

At the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2021, Werewolf presented data from a surrogate WTX-613 INDUKINE molecule that demonstrated tumor stasis lasting beyond the treatment phase, efficiently blocked tumor growth, activated NK and CD8+ cell responses and induced antigen-presenting cell and effector cell markers in preclinical models.

Transaction Details
Under the terms of the transaction, Jazz has secured exclusive global rights to WTX-613. Jazz will make an upfront payment of $15 million to Werewolf, and Werewolf is eligible to receive development, regulatory and commercial milestone payments of up to $1.26 billion. Pending approval, Werewolf is eligible to receive a tiered, mid-single-digit percentage royalty on net sales of WTX-613.

On April 7, 2022 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of MasterKey therapies, reported that its President and Chief Executive Officer, David M. Epstein, Ph.D., will present an update on the Company’s progress at the Canaccord Genuity Horizons in Oncology Virtual Conference being held on Thursday, April 14, 2022 at 10:00 a.m. ET (Press release, Black Diamond Therapeutics, APR 7, 2022, View Source [SID1234611636]).

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A live webcast of the panel discussion can be accessed by visiting the investor relations section of the Company’s website, www.blackdiamondtherapeutics.com. A replay of the panel discussion will also be available and archived on the site for 90 days.

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.