On December 14, 2021 Bio-Techne Corporation (NASDAQ: TECH), a global life sciences company providing innovative tools and bioactive reagents for the research and clinical diagnostic communities, reported it has entered into an option agreement with Wilson Wolf Corporation (Press release, Bio-Techne, DEC 14, 2021, View Source [SID1234597084]). The agreement includes a potential 20% ownership investment in Wilson Wolf upon its achievement of approximately $100 million in revenue or $50 million in earnings before interest, taxes, depreciation, and amortization (EBITDA) as well as the opportunity to fully acquire the company upon its achievement of approximately $225 million in revenue or $135 million in EBITDA.

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Founded in 1998, Wilson Wolf is headquartered in St. Paul, Minnesota and is a leader in the development, manufacture, and commercialization of cell culture technologies, including its Gas Permeable Rapid Expansion (G-Rex) product line. G-Rex devices are a critical component of the cell therapy workflow, serving as a vessel to create high quality cells that can reconstitute the immune system’s capacity to fight disease. G-Rex was created specifically to produce immune cells such as T cells, natural killer cells, and hematopoietic stem cells. With a revolutionary design, G-Rex provides an easy, fast and cost-effective method for scaling cell therapies in the least amount of space.

In 2020, Wilson Wolf, Bio-Techne and Fresenius Kabi announced the formation of the ScaleReady joint venture, bringing together tools and technologies for cell culture, cell activation, gene editing and cell processing. ScaleReady is empowering the field of cell and gene therapy by delivering a simple, scalable, and versatile manufacturing platform for cell and gene therapies.

"The explosive growth in cell and gene therapy (CGT) is reminiscent of the monoclonal antibody field that Bio-Techne was founded on. CGT’s lifesaving technology is now being touted as the 4th pillar of cancer treatment. The key to CGT lies in manufacturing simplicity, and we believe Wilson Wolf’s G-Rex technology has the necessary attributes to bring CGT manufacturing to the simplest state while delivering the most robust cancer killing cells," said Chuck Kummeth, President and Chief Executive Officer of Bio-Techne. "Having interacted with Wilson Wolf for several years, I continue to be impressed by their vision, ability to execute, and market penetration. This strengthened relationship accelerates our mutual goal of simplifying CGT manufacturing by leveraging G-Rex technology and Bio-Techne’s GMP proteins and antibodies, instrumentation, media, gene editing, aggregation, and selection solutions. Closer ties with Wilson Wolf also enhances the capacity of our ScaleReady joint venture to provide the rapidly expanding field of CGT with the simplest and most versatile manufacturing platform."

"Wilson Wolf is driven to simplify Cell and Gene Therapy manufacturing and increase the presence of lifesaving drugs that are fundamentally improving the way cancer and other diseases are treated. Bio-Techne is equally driven, and their portfolio of broad-based solutions are directly suited to advancing our common cause," said John Wilson, Founder and Chief Executive Officer of Wilson Wolf. "The rapidly growing market adoption of our G-Rex technology and explosive growth of this incredible industry makes this the right time for Wilson Wolf to deepen its relationship with Bio-Techne. ScaleReady, our joint venture with Bio-Techne and Fresenius Kabi, will continue to be the catalyst through which we will bring CGT manufacturing to the ultimate state of simplicity. From a personal perspective, it’s exciting to envision all the ways this enhanced bond between ScaleReady partners strengthens our capacity to deliver hope to cancer patients, one G-Rex device at a time."

On December 14, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported new analyses on the ongoing studies of HMPL-523 presented at the 63rd American Society for Hematology’s (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, held virtually and in person at the Georgia World Congress Center in Atlanta, Georgia (Press release, Hutchison China MediTech, DEC 14, 2021, View Source [SID1234597083]).

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Further details of the presentations are as follows:

Title:

Safety, Pharmacokinetics, and Preliminary Efficacy of HMPL-523 in Adult Patients with Primary Immune Thrombocytopenia: A Randomized, Double-Blind and Placebo-Controlled Phase Ib Study

Presenter:

Renchi Yang, MD, Hematology Hospital of the Chinese Academy of Medical Sciences

Session:

311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Treatment of Immune Thrombocytopenia

Abstract No.:

149895

Date & Time:

Saturday, December 11, 2021 9:30am – 11am ET

Location:

Georgia World Congress Center, C101 Auditorium and virtually

As of data cutoff date of September 30, 2021, a total of 34 patients were randomized to receive HMPL-523 and 11 patients to placebo. Among 16 patients who were randomized to receive the recommended phase II ("RP2D") dose of 300mg once daily, 11 patients (68.8%) experienced response as defined by at least one incident of platelet count being ≥ 50×109/L in the initial 8-week double blinded phase of the study, compared to one out of 11 patients (9.1%) randomized to receive placebo. During the subsequent 16-week open-label phase of the study, one additional patient initially randomized to receive the RP2D experienced a response. Four patients randomized to placebo crossed over to receive treatment at RP2D after the initial 8-week double blinded phase of the study; all four of these patients experienced response. In total, 16 out of 20 patients (80%) experienced response during both phases of the study. Durable response, defined as platelet count being ≥ 50×109/L in at least 4 out of 6 last scheduled visits, were reported in 8 out of 20 patients (40%) who received RP2D in both phases of the study.

Safety data were presented for all 41 patients who received treatment at all doses, regardless of whether they were initially randomized to receive active treatment or crossed over during the open-label extension phase of the study. The median duration of treatment was 142 days (range: 23-170). No patients discontinued treatment due to treatment-related adverse events ("TRAE"), and no cases of treatment-related serious adverse events ("SAE") were reported. There were 30 patients (73%) who experienced TRAEs, including 3 (7.3%) who experienced grade 3 or above TRAEs, one of whom received the RP2D. No TRAEs of grade 3 or above occurred in more than one patient.

These results supported the initiation of a Phase III registration study of HMPL-523 in adult patients with primary immune thrombocytopenia ("ITP"), ESLIM-01. The first patient in this study received their first dose on October 27, 2021. Additional details may be found at clinicaltrials.gov, using identifier NCT05029635.

Title:

Preliminary Results from a Phase I Study of HMPL-523, a Selective, Oral Syk Inhibitor, in Patients with Relapsed or Refractory Lymphoma

Presenter:

Paolo Strati, MD, The University of Texas MD Anderson Cancer Center

Session:

623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemio­logical: Poster II

Abstract No.:

2432

Date & Time:

Sunday, December 12, 2021 6:00pm – 8:00pm ET

Location:

Georgia World Congress Center, Hall B5 and virtually

As of data cutoff date of August 25, 2021, 21 patients received a median of two cycles of treatment (range: 1-19). Among 16 response-evaluable patients, 4 responses were seen in patients in the 400-800 mg cohorts totaling 10 patients. Nine patients experienced disease progression, three in the 400-800mg cohorts and six in the 100-200mg cohorts.

Among 21 enrolled patients, 17 (81.0%) patients experienced TRAEs, including 7 (33.3%) who experienced grade 3 or above TRAEs. Specific to TRAE at grade 3 or above, neutropenia, which occurred in 2 patients, was the only TRAEs of grade 3 or above to have occurred in more than one patient. SAEs were reported in 6 patients (28.6%). Adverse events leading to discontinuation were reported in 2 (9.5%) patients. 7 patients withdrew from the study for reasons other than progressive disease.

These results support progressing HMPL-523 into the ongoing dose expansion phase of the study to evaluate its safety and efficacy in multiple subtypes of B-cell and T-cell lymphoma at the R2PD of 700 mg.

About HMPL-523

HMPL-523 is a novel, investigational, selective small molecule inhibitor for oral administration targeting spleen tyrosine kinase, also known as Syk. Syk is a major component in B-cell receptor signaling and is an established target for the treatment of multiple subtypes of B-cell lymphomas and autoimmune disorders.

HUTCHMED currently retains all rights to HMPL-523 worldwide. The ESLIM-01 Phase III trial is underway to evaluate the efficacy and safety of HMPL-523 in treating adult patients with primary ITP, an autoimmune disorder that can lead to increased risk of bleeding. Additional details may be found at clinicaltrials.gov, using identifier NCT05029635. HMPL-523 is also being studied in indolent non-Hodgkin’s lymphoma and multiple subtypes of B-cell malignancies in China (NCT02857998), the U.S. and Europe (NCT03779113). A trial to study HMPL-523 in patients with warm autoimmune hemolytic anemia (wAIHA), another autoimmune disorder, is also planned.

On December 14, 2021 Carina Biotech reported that it has entered a license agreement with Bayerische Patentallianz (BayPAT) to the CXCR6-transduced CAR-T cell technology developed at the University Hospital of Ludwig-Maximillian University of Munich (LMU) (Press release, Carina Biotech, DEC 14, 2021, View Source [SID1234597080]).

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The agreement grants Carina a worldwide exclusive license to use the CXCR6 chemokine receptor technology patents in the field of CAR-T cells.

Carina’s proprietary Multi-functional Chemokine Receptor Platform, headed by Carina’s Professor Shaun McColl (pictured) creates CAR-T cells expressing chemokine receptors that drive CAR-T cells to ‘home in’ on specific cancer cells including colorectal, prostate, breast and lung cancers.

Access to the patents covering the CXCR6 technology developed at LMU both expands and complements Carina’s Chemokine Receptor Platform, enabling and enhancing CAR-T cell homing to certain solid tumour types, resulting in greater CAR-T activity.

Dr Deborah Rathjen, Carina’s CEO, commented: "Carina has a world leading, proprietary platform for the generation of human CAR-T cells to treat cancer. Our precision approach is based on over 30 years of research on T cells and immunity and chemokine and chemokine receptor biology. CAR-T therapy is now an accepted immunotherapy approach for blood cancers. The challenge, which we believe our Multi-functional Chemokine Receptor Platform overcomes, is to provide rapid access to solid cancers. We are delighted to have licensed this patent family from BayPAT and the LMU because the CXCR6 technology expands, in a complementary way, the chemokine receptor technology we can access to create next generation cell therapies to treat cancer."

"Carina is making rapid progress towards becoming a clinical stage company with our LGR5 directed CAR-T for the treatment of metastatic colorectal (bowel) cancer tracking well, with an anticipated IND filing and the start of a clinical trial next year. This CAR-T has delivered impressive preclinical results and we are excited by its prospects for treating a range of solid cancer types in addition to colorectal cancer," Dr Rathjen added.

Solid cancers secrete small proteins called chemokines. Each cancer has a specific chemokine secretion ‘profile’, which forms a chemokine concentration gradient around solid cancers. Certain cancers – such as colorectal, prostate, breast and lung cancers – upregulate a chemokine called CXCL16, which binds to the chemokine receptor CXCR6.

Under the agreement, Carina will develop CAR-T cells that express CXCR6, enabling Carina’s CAR-T cells to migrate along the CXCL16 chemokine gradient to certain cancers, enter the tumours more rapidly and then efficiently kill the cancer cells.

"We are very happy that this highly innovative CXCR6 chemokine receptor technology will be further developed by experts in the area of CAR-T therapies to ensure that the full potential of that technology will be exploited to benefit patients to fight their cancer," added Dr Robert Phelps, BayPAT’s CEO.

Professor Sebastian Kobold MD, lead inventor of the CXCR6 technology at LMU University Hospital, said: "CXCR6 is a receptor with unique properties and biology that can confer to therapeutic T cells decisive advantages to enter solid tumour tissue. We have demonstrated the potential utility in combination with CAR-T cells as well as its biological function in cancer in two seminal publications in Nature Biomedical Engineering and Cell this year. We are excited to have Carina Biotech now a dedicated partner, who will translate this technology into clinical trials."

On December 14, 2021 Exelixis, Inc. (Nasdaq: EXEL) and Aurigene Discovery Technologies Limited (Aurigene) reported that Exelixis has exercised its exclusive option under the companies’ July 2019 agreement to in-license XL114 (formerly AUR104), a novel anti-cancer compound that inhibits the CARD11-BCL10-MALT1 (CBM) signaling pathway, which promotes lymphocyte survival and proliferation (Press release, Aurigene Discovery, DEC 14, 2021, View Source [SID1234597078]). Exelixis has now assumed responsibility for the future clinical development, commercialization and global manufacturing of XL114. Following the U.S. Food and Drug Administration’s (FDA) recent acceptance of its Investigational New Drug (IND) application, Exelixis will soon initiate a phase 1 clinical trial evaluating XL114 monotherapy in patients with Non-Hodgkin’s lymphoma (NHL). At the American Association of Cancer Research Annual Meeting in April of this year, Aurigene presented preclinical data (Abstract 1266) demonstrating that XL114 exhibited potent anti-proliferative activity in a large panel of cancer cell lines ranging from hematological cancers to solid tumors with excellent selectivity over normal cells. In addition, oral dosing of XL114 resulted in significant dose-dependent tumor growth inhibition in diffuse large B-cell lymphoma (DLBCL) and colon carcinoma models.

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XL114 is the second molecule that Exelixis in-licensed from Aurigene under the companies’ July 2019 collaboration, option and license agreement. Exelixis previously exercised its option to in-license XL102, a potent, selective and orally bioavailable inhibitor of cyclin-dependent kinase 7 (CDK7), from Aurigene in December 2020 and initiated a phase 1 trial of XL102 as a single agent and in combination with other anti-cancer agents in patients with advanced or metastatic solid tumors in January 2021.

"We are pleased that our agreement with Aurigene has generated a second promising compound that warrants advancement into clinical development and believe the collaboration will continue to play an important role in expanding our pipeline," said Peter Lamb, Ph.D., Executive Vice President, Scientific Strategy and Chief Scientific Officer, Exelixis. "XL114 has shown potent anti-proliferative activity in lymphoma cell lines that have aberrant activation of the CBM signaling pathway and may have a differentiated profile and potential as a best-in-class molecule that could improve outcomes for patients with Non-Hodgkin’s lymphoma and other hematologic cancers."

XL114 was identified to have anti-proliferative activity in cell lines with constitutive activation of CBM signaling, including activated B-cell-like DLBCL (ABC-DLBCL), mantle cell lymphoma and follicular lymphoma cell lines. Further characterization of XL114 in cell-based assays demonstrated a functional role in B-cell (BCR) signaling pathways. Additionally, XL114 showed dose-dependent tumor growth inhibition in an ABC-DLBCL mouse xenograft tumor model. In preclinical development, XL114 also demonstrated a high degree of selectivity against a broad safety pharmacology panel of enzymes and receptors. While the precise molecular mechanism underlying XL114’s function in repressing BCR signaling and MALT1 activation has yet to be characterized, the fatty acid-binding protein 5 (FABP5) has been identified as a prominent XL114-binding target.

"XL114 is the second molecule that Exelixis has opted to in-license under our July 2019 agreement, underscoring the significant potential of our approach to the discovery and preclinical development of innovative cancer therapies that target novel mechanisms of action," said Murali Ramachandra, Ph.D., Chief Executive Officer, Aurigene. "Exelixis has a track record of success in the clinical development and commercialization of anti-cancer therapies that provide patients with important new treatment options, and we are pleased that the continued advancement of XL114 will be supported by the company’s extensive clinical, regulatory and commercialization infrastructure."

Under the terms of the July 2019 agreement, Exelixis made an upfront payment of $10 million for exclusive options to obtain an exclusive license from Aurigene to three preexisting programs, including the compounds now known as XL102 and XL114. In addition, Exelixis and Aurigene initiated three Aurigene-led drug discovery programs on mutually agreed upon targets, in exchange for an additional upfront payment of $2.5 million per program. The collaboration was expanded in 2021 to include three additional early discovery programs. Exelixis is also contributing research funding to Aurigene to facilitate discovery and preclinical development work on all nine programs. Exelixis may exercise its option for a program at any time up until the first IND for the program becomes effective. Having exercised options on two programs thus far (XL102 and XL114), if and when Exelixis exercises a future option, it will make an option exercise payment to Aurigene and assume responsibility for that program’s future clinical development and commercialization including global manufacturing. To exercise its option for XL114, Exelixis will make an option exercise payment to Aurigene of $10 million. Once Exelixis exercises its option for a program, Aurigene will be eligible for clinical development, regulatory and sales milestones, as well as royalties on future potential sales of the compound. Under the terms of the agreement, Aurigene retains limited development and commercial rights for India and Russia.

On December 14, 2021 Idera Pharmaceuticals, Inc. ("Idera," the "Company," "we," "us," and "our") (Nasdaq: IDRA) reported clinical updates regarding tilsotolimod, its synthetic Toll-like receptor 9 agonist (Press release, Idera Pharmaceuticals, DEC 14, 2021, View Source [SID1234597077]).

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ILLUMINATE-206 Trial for the Treatment of Previously Treated Patients with Immunotherapy-Naïve Micro-Satellite Stable Colorectal Cancer (MSS-CRC)
Preliminary data from the second 10 patients dosed in the safety cohort of ILLUMINATE-206, which involves tilsotolimod in combination with ipilimumab and nivolumab, showed a safety profile consistent with the first 10 patients in ILLUMINATE-206 and with prior studies. Eight patients had a post-baseline disease assessment evaluated per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). Of those, one patient experienced Stable Disease (SD) with disease control for more than six months; the remaining patients experienced Progressive Disease (PD). However, one of the RECIST v1.1 PD patients was determined to have experienced pseudo-progression, meaning that the initial increase from baseline in overall tumor burden was followed by a decrease from baseline in overall tumor burden. At the most recent disease assessment, the total decrease from baseline was 46.2%, which is considered an Immune-Related Partial Response (irPR) by Immune-Related RECIST (irRECIST). Per protocol, the patient is continuing in active treatment. No further enrollment in ILLUMINATE-206 is planned at this time.

Collaboration with AbbVie for the Treatment of Head and Neck Squamous Cell Carcinoma
AbbVie Inc. ("AbbVie") is conducting a Phase 1b study for treatment of patients with recurrent/metastatic head and neck squamous cell carcinoma with ABBV-368 plus tilsotolimod and other therapy combinations. AbbVie has discontinued further patient enrollment in the study; this decision was not related to safety concerns. Current patient treatment and follow-up is ongoing. AbbVie is solely responsible for the conduct of the study, with Idera contributing tilsotolimod supply.

Investigator-Sponsored Trial for the Intradermal Treatment of Melanoma
The VU University Medical Center (VUmc) Amsterdam, which is conducting a randomized, controlled trial of a single, intradermal injection of tilsotolimod at the primary melanoma excision site in 214 patients, recently shared with the Company early translational data supporting the mechanism of action of tilsotolimod. "As expected, immune activation, including elevated frequencies of key dendritic cells, was seen in early analysis by flow cytometry of sentinel lymph node biopsies collected seven days post-injection," said Dr. Tanja de Gruijl of VUMC. "These data are consistent with previously reported translational data relating to tilsotolimod in other pre-clinical and clinical settings. We are eager to see if this evidence of immune system stimulation will translate to clinical benefit in this patient population." Enrollment in this study is ongoing.

Investigator-Sponsored Trial for the Treatment of Advanced Cancers
The Gustave Roussy Cancer Campus in Paris is conducting an open-label, Phase 1b study of intratumoral tilsotolimod in combination with intratumoral ipilimumab and intravenous nivolumab in advanced cancers, including non-squamous cell lung cancer, refractory advanced melanoma, and MSS-CRC. Dosing in Part A of the study, which involved 24 patients across two different dose frequencies of ipilimumab and tilsotolimod, is complete; patient follow up is ongoing.

Out-Licensing Consideration
"While our clinical trials with tilsotolimod have not yet translated into a new treatment alternative for patients, data supporting tilsotolimod’s mechanism of action and encouraging safety profile from across the array of pre-clinical and clinical work to date, together with its intellectual property protection, are noteworthy," stated Vincent Milano, Idera’s Chief Executive Officer. "As a result, we will consider an out-licensing arrangement for tilsotolimod so that its full potential may continue to be explored on behalf of patients who do not respond to traditional immunotherapy. We also continue both to preserve cash and to identify and explore potential development or commercial-stage assets for Idera’s portfolio, and we are encouraged by the opportunities presented to us."

About Tilsotolimod (IMO-2125)
Tilsotolimod is an investigational, synthetic Toll-like receptor 9 agonist. Intratumoral injection of tilsotolimod has been shown to promote both innate (Type-I IFN, antigen presentation) and adaptive (T cells) immune activation. Tumors with an active immune response appear to respond better to checkpoint inhibitors (CPIs) than those that exclude or inhibit anti-tumor immune cells. Tilsotolimod in combination with CPIs may cause regression of locally injected and distant tumor lesions and increase the number of patients who benefit from immunotherapy.

Tilsotolimod is being evaluated in multiple tumor types and in combination with multiple CPIs. For more information on tilsotolimod trials, please visit www.ClinicalTrials.gov.