On December 2, 2020 Tubulis, WuXi STA and WuXi Biologics reported a strategic collaboration to manufacture and advance Tubulis’ next generation antibody-drug conjugates (ADCs) towards IND-enabling studies (Press release, Tubulis, DEC 2, 2020, View Source [SID1234572079]). Tubulis has developed a dual platform approach to generate uniquely matched and disease-specific ADCs that combine selective antibodies with effective payloads. This approach has demonstrated superior stability and efficacy in preclinical studies. The partnership with WuXi Biologics ("WuXi Bio") (2269.HK), a global company with leading open-access biologics technology platforms and STA Pharmaceutical, a WuXi AppTec Company, (WuXi STA), will support the scale-up of the manufacturing process to a global clinical standard. The first program from Tubulis’ pipeline the companies will collaborate on is TUB-010, a uniquely matched, highly stable and efficient protein-drug conjugate designed to treat patients with lymphoma.

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Under the terms of the agreement, WuXi Biologics and WuXi STA will become the Contract Development and Manufacturing Organization (CDMO) partners for Tubulis. WuXi Biologics and WuXi STA will perform scale-up, process development and GMP manufacturing for the ADC product intermediates, with WuXi STA focused on the linker and payload and WuXi Biologics on the monoclonal antibody (mAb) and the enzyme used in Tubulis´ proprietary Tub-tag technology. WuXi Biologics subsequently will conduct process development and GMP bioconjugation to produce the drug substance and the final drug product formulation and fill for final preclinical toxicology studies. WuXi Biologics will also supply product batches for clinical evaluation. Financial details of the collaboration were not disclosed.

"As leaders in manufacturing for innovative technology platforms, WuXi Biologics and WuXi STA provide world-class capabilities for the development and production of our ADCs," said Dr. Dominik Schumacher, CEO of Tubulis. "For our uniquely versatile and customizable ADC technology portfolio, it was important to partner with CDMOs that have extensive experience with ADCs and offer the opportunity for a long-term partnership at the highest quality level. We are rapidly moving towards the clinic with our first ADC candidate and are excited to have entered this partnership, which will enable the further maturation of our pipeline."

"Tubulis requires single-source technology platforms, scientific expertise and state-of-the-art facilities set to the highest global quality standards. This is why we are thrilled to be selected for this project," remarked Dr. Chris Chen, CEO of WuXi Biologics. "This collaboration is a perfect illustration of the value that WuXi Biologics provides to innovative companies worldwide. Bioconjugates like TUB-010 are highly complex and require high levels of expertise and integration across the entire supply chain. We will leverage our advanced development platforms, large scientific teams dedicated to ADCs and industry-leading development timelines to bring TUB-010 towards the clinic."

"We are honored that Tubulis selected our organization to help bring this novel therapeutic towards the clinic with the goal of benefiting patients worldwide," commented Dr. Minzhang Chen, CEO of WuXi STA. "I am confident that WuXi STA’s leading capability and capacity for high potency API, along with our high quality standards in meeting global regulatory requirements, will provide the strongest support for ADC linker and payload development and manufacturing. Our strong connection and past experience working with WuXi Biologics on ADC therapeutics, and our shared commitment to providing seamless project management and one-stop services, will ensure that together we can develop and manufacture TUB-010 efficiently."

Tubulis recently completed a €10.7 million Series A to expand the therapeutic potential of ADCs and to advance its uniquely versatile and customizable ADC technology portfolio. The company utilizes two proprietary technologies to tackle limitations of currently approved ADCs, which include stability and payload-driven toxicity. With the P5 conjugation, Tubulis employs a cysteine-selective conjugation that enables the generation of ultra-stable ADCs with unprecedented linker stability and chemical flexibility, enabling rapid lead identification. The second technology, the human-derived Tub-tag platform, modulates the antibody to provide a highly beneficial microenvironment for the payload, thereby adding a significant amount of stability to the ADC. By tailoring the ADCs to the respective indication, Tubulis develops innovative compounds to treat cancer and beyond.

On December 3, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX) reported the publication of data from a Phase 2 study evaluating umbralisib, the Company’s investigational once daily, oral, dual inhibitor of PI3K-delta and CK1-epsilon, in patients with chronic lymphocytic leukemia (CLL) who are intolerant to prior BTK or PI3K-delta inhibitor therapy, in Blood, the Journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, TG Therapeutics, DEC 2, 2020, View Source [SID1234572077]).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "We are extremely encouraged by the data published today demonstrating that umbralisib monotherapy induced durable responses and enhanced progression-free survival in patients who were unable to tolerate their prior BTKi or PI3K delta therapy. Despite many advances in the treatment of CLL in recent years, early termination of kinase inhibitors due to tolerability is an emerging issue leaving too many CLL patients without adequate therapy." Mr. Weiss continued, "With our rolling BLA submission recently initiated for ublituximab in combination with umbralisib for patients with CLL, and our ongoing clinical studies evaluating triplet regimens in this disease, we remain committed to addressing unmet needs in CLL."

The manuscript includes data from 51 chronic lymphocytic leukemia (CLL) patients who were previously treated with and became intolerant to prior BTK or PI3K inhibitor therapy (44 BTK intolerant and 7 PI3K intolerant patients). Patients were treated with 800 mg of umbralisib once daily. The primary endpoint was progression-free survival (PFS). Safety data was available from all patients enrolled (n=51). Key highlights from this manuscript include:

The most common (≥5%) grade ≥3 AEs were neutropenia (18%), leukocytosis (14%), thrombocytopenia (12%), pneumonia (12%), and diarrhea (8%).
Six patients (12%) discontinued umbralisib due to an AE. Eight patients (16%) had dose reductions and were successfully re‐challenged allowing them to continue on umbralisib.
Median progression free survival (PFS) was 23.5 months (95% CI 13.1‐not estimable).
As of the data cut off, 58% of patients had been on umbralisib for a longer duration than their prior kinase inhibitor.
These data are described further in the manuscript entitled, "Phase 2 Study of the Safety and Efficacy of Umbralisib in Patients with CLL Who Are Intolerant to BTK or PI3Kδ Inhibitor Therapy," which was published online in the First Edition section of Blood, the Journal of the American Society of Hematology (ASH) (Free ASH Whitepaper). The online version of the article can be accessed at www.bloodjournal.org.

On December 2, 2020 Immatics N.V. (NASDAQ: IMTX; "Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell redirecting cancer immunotherapies, reported financial results and provided a business update for the quarter ended September 30, 2020 (Press release, Immatics, DEC 2, 2020, View Source [SID1234572076]).

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"The third quarter was highlighted by meaningful progress in our ACTengine IMA200 clinical trial series. Seven clinical sites in Germany and the US are now initiated and screening patients. These advancements mark critical steps towards delivering our clinical milestones for the coming year including reporting on initial data for ACTengine patients in dose escalation in Q1," said Harpreet Singh, Ph.D., CEO of Immatics. "In conjunction with our clinical and operational progress, we are pleased to further strengthen the Company’s capabilities with the appointments of both Eliot Forster to the Board and Arnd Christ as Chief Financial Officer."

Third Quarter 2020 and Subsequent Company Progress

Adoptive Cell Therapy Programs

ACTengine IMA200 Series – Immatics continued to select and initiate additional clinical trial sites in Germany and the US. The increased patient enrollment seen at sites in Germany was able to mitigate the impact of the global COVID-19 pandemic at US sites. These patients are expected to be treated within the fourth quarter this year, moving Immatics towards delivering the clinical milestones for ACTengine in the coming year. Combined initial data readout for ACTengine programs, IMA201, IMA202 and IMA203, continues to be expected in Q1 2021. Reported initial data will focus on safety and pharmacodynamic data including engraftment level, persistence and molecular phenotype of infused T cells as well as clinical change of target tumor lesions.
ACTengine IMA204 – Immatics presented preclinical data from the ACTengine cell therapy program targeting the tumor microenvironment on September 10. IMA204 is directed at a novel target, COL6A3 exon 6, which is highly expressed in the tumor stroma of a variety of solid cancers. An affinity-enhanced TCR candidate directed to this target demonstrated full functionality in CD8+ and CD4+ T cells indicating that this TCR could be employed in a next-generation ACTengine approach without the need of CD8 co-receptor transduction. Submission of an Investigational New Drug (IND) application to the US Food and Drug Administration (FDA) for IMA204 remains anticipated for 2021.
ACTolog IMA101 – On November 10, Immatics presented topline data from its clinical pilot trial IMA101, a personalized multi-target ACT approach using the patient’s own, non-engineered T cells. The trial demonstrated feasibility and tolerability of this approach as well as very high persistence of endogenous T cells directed against defined pHLA targets. Clinical course observations in patients treated with T cells directed at the tumor stroma target COL6A3 exon 6 warrant further exploration of this target within ACTengine. The results also support further development of a multi-target approach using multiple engineered TCRs simultaneously in ACTengine.

TCR Bispecifics Programs

IMA401 – A preclinical data update from Immatics’ first TCR Bispecifics (TCER) program on October 29, delivered pre-clinical proof-of-concept for IMA401 demonstrating complete remission of transplanted human tumors in mice as well as favorable CMC characteristics. The IMA401 cancer target, an HLA-A*02-bound peptide derived from both MAGEA4 and MAGEA8, showed more than 5-fold higher target copy numbers per tumor cell than a commonly used target peptide derived from MAGEA4. Submission of the IMA401 IND/IMPD application remains expected by the end of 2021.
Corporate Development

Management and Board of Directors Updates

Eliot Forster, Ph.D., joined Immatics’ Board of Directors as a new member in September 2020. He brings to Immatics extensive experience, including leadership of trailblazing biopharmaceutical companies in the field of immuno-oncology as well as other therapeutic areas.
In October 2020, Arnd Christ joined Immatics’ leadership team as Chief Financial Officer (CFO). He was previously the CFO of Nasdaq-listed InflaRx and brings nearly two decades of experience serving as the CFO of both private and public biotechnology companies.

Collaborations and Strategic Alliances

On August 6, Immatics announced the extension of its strategic alliance with UTHealth. The continued collaboration will provide Immatics exclusive access to three cGMP suites enabling manufacturing and supply of its ACT products for current and upcoming Phase 1 clinical trials in the US and Europe for an additional four years until end of 2024.

Third Quarter 2020 Financial Results

Cash Position: Cash and cash equivalents as well as other financial assets sum up to €259.3 million ($303.6 million1) as of September 30, 2020 compared to €86.1 million ($100.8 million1) as of June 30. The increase is mainly due to the business combination with ARYA Sciences Acquisition Corporation completed in July 2020 (ARYA merger) and the concurrent PIPE Financing.

Revenue: Total revenue, consisting of revenue from collaboration agreements, was €7.8 million ($9.1 million1) for the three months ended September 30, 2020, compared to €5.1 million ($6.0 million1) for the three months ended September 30, 2019.

Research and Development Expenses: R&D expenses were €17.5 million ($20.5 million1) for the three months ended September 30, 2020, compared to €10.2 million ($11.9 million1) for the three months ended September 30, 2019. The increase is mainly due to increased share-based compensation (€4.6 million; $5.4 million1).

General and Administrative Expenses: G&A expenses were €9.2 million ($10.8 million1) for the three months ended September 30, 2020, compared to €2.7 million ($3.2 million1) for the three months ended September 30, 2019. The increase is mainly due to increased share-based compensation (€3.6 million; $4.2 million1) as well as one-time transaction costs of the NASDAQ listing in connection with the ARYA merger in July.

Net Loss: Net loss was €177.1 million ($207.3 million1) for the three months ended September 30, 2020, compared to €5.0 million ($5.9 million1) for the three months ended September 30, 2019 of which €152.8 million ($178.9 million1) resulted from a one-time, non-cash expense in connection with the ARYA merger. The main part of this €152.8 million ($178.9 million1) non-cash expense resulted from the share price increase between signing and closing of the ARYA merger. For detailed information, please refer to Note 9 of the Notes to the Financial Statements.

Upcoming Investor Conferences

Piper Sandler Healthcare Conference – December 1-3, 2020
10th Annual SVB Leerink Global Healthcare Conference – February 24-26, 2021

To see the full list of events and presentations, visit www.investors.immatics.com/events-presentations.

Full financial statements can be found in the current report on Form 6-K filed with the Securities and Exchange Commission (SEC) and published on the SEC website under View Source

1 All amounts translated using the exchange rate published by the European Central Bank in effect as of September 30, 2020 (1 EUR = 1.1708 USD).

On December 2, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has approved Gavreto (pralsetinib) for the treatment of adult and paediatric patients 12 years of age and older with advanced or metastatic rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC) who require systemic therapy, or with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) (Press release, Hoffmann-La Roche, DEC 2, 2020, View Source [SID1234572072]). These indications were approved under the FDA’s accelerated approval programme based on data from the phase I/II ARROW study. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

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"We are proud to partner with Blueprint Medicines to bring this important new option to people with certain types of RET-altered thyroid cancer," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "Gavreto is now approved across multiple RET-altered tumour types, underscoring our commitment to advancing personalised healthcare with treatments that target the underlying biology of each person’s cancer."

Approximately 10-20% of people with papillary thyroid cancer (the most common type of thyroid cancer)1 have RET fusion-positive tumours,2 and roughly 90% of people with advanced MTC (a rare form of thyroid cancer) carry RET mutations.3 Biomarker testing for RET fusions and mutations can help identify people who are eligible for treatment with Gavreto.

The approvals are based on results from the phase I/II ARROW study, which demonstrated durable clinical activity in people with or without prior therapy and regardless of RET alteration genotypes.4 Treatment with Gavreto led to an overall response rate (ORR) of 60% (95% CI: 46%, 73%) in 55 people with RET-mutant metastatic MTC previously treated with cabozantinib and/or vandetanib, and the median duration of response (DoR) was not reached (95% CI: 15.1 months, not estimable).2 In 29 people with cabozantinib- and vandetanib-naïve RET-mutant advanced MTC who were determined to be not eligible for standard therapies, the ORR was 66% (95% CI: 46%, 82%), and the median DoR was not reached (95% CI: not estimable, not estimable).4 In nine people with RET fusion-positive metastatic thyroid cancer, Gavreto demonstrated an ORR of 89% (95% CI: 52%, 100%), and the median DoR was not reached (95% CI: not estimable, not estimable).4 In ARROW trial patients across RET-altered tumour types, the most common adverse reactions (≥25%) were constipation, increased blood pressure (hypertension), fatigue, musculoskeletal pain and diarrhoea.4

The FDA reviewed and approved the application under its Real-Time Oncology Review (RTOR) pilot programme, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. In September, the FDA also granted accelerated approval to Gavreto for the treatment of adults with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. In addition, the FDA granted Breakthrough Therapy Designation to Gavreto for the treatment of RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments and for RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy.

Gavreto is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations.

About the ARROW study5
ARROW (NCT03037385) is a phase I/II, open-label, first-in-human study designed to evaluate the safety, tolerability and efficacy of Gavreto, administered orally in people with rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), RET-mutant medullary thyroid cancer (MTC), RET fusion-positive thyroid cancer and other RET-altered solid tumours. The trial consists of two parts: a dose escalation portion, which is complete, and an expansion portion in people treated with 400 mg of Gavreto, once-daily. ARROW is being conducted at multiple sites across the United States, European Union and Asia.

About RET-altered cancers
RET gene alterations, such as fusions and mutations, are key disease drivers in many types of cancer, including NSCLC and several types of thyroid cancers. Approximately 10-20% of people with papillary thyroid cancer (the most common type of thyroid cancer)1 have RET fusion-positive tumours,2 and roughly 90% of people with advanced MTC (a rare form of thyroid cancer) carry RET mutations.3 In NSCLC, RET fusions represent approximately 1-2% of patients.6 Oncogenic RET fusions also are observed at low frequencies in cholangiocarcinoma, colorectal, neuroendocrine, ovarian, pancreatic and thymus cancers.

About Gavreto
Gavreto is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations, regardless of the tissue of origin. Preclinical data have shown that Gavreto inhibits primary RET fusions and mutations that cause cancer in subsets of patients, as well as secondary RET mutations predicted to drive resistance to treatment. Blueprint Medicines and Roche are co-developing Gavreto for the treatment of patients with various types of RET-altered cancers.

Blueprint Medicines and Roche are co-developing Gavreto globally, excluding Greater China.* Blueprint Medicines and Genentech, a wholly owned member of the Roche Group, will co-commercialise Gavreto in the US and Roche has exclusive commercialisation rights for Gavreto outside of the US, excluding Greater China.*

On December 1, 2020 BridgeBio Pharma, Inc. (NASDAQ: BBIO), a clinical-stage biopharmaceutical company founded to discover, create, test and deliver meaningful medicines for patients with genetic diseases and cancers with clear genetic drivers, and affiliate QED Therapeutics reported that the U.S. Food and Drug Administration (FDA) has accepted their New Drug Application (NDA) for infigratinib, an oral FGFR1-3 selective inhibitor, for individuals with cholangiocarcinoma, or cancer of the bile ducts (Press release, BridgeBio, DEC 1, 2020, View Source [SID1234576220]).

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The NDA has been granted Priority Review designation and is being reviewed under the Real-Time Oncology Review (RTOR) pilot program, an initiative of the FDA’s Oncology Center of Excellence designed to expedite the delivery of safe and effective cancer treatments to patients. Additionally, BridgeBio will submit for review in Australia and Canada under Project Orbis, an initiative of the FDA’s Oncology Center of Excellence that allows for concurrent submission and review of oncology drugs among participating international regulatory agencies.

Cholangiocarcinoma, a cancer of the bile ducts of the liver, is a serious and often fatal disease which affects approximately 20,000 people in the United States and European Union each year. FGFR2 genetic aberrations are present in approximately 15% to 20% of people who have this disease. Currently, treatment options are limited, and the five-year survival rate is only 9%.

"We want to thank the patients, families, scientists, physicians and all others involved who helped us move this NDA forward. At BridgeBio we believe that every minute counts for patients and their families, and we are eager to help as many people suffering from cholangiocarcinoma as possible – as quickly as possible," said BridgeBio CEO and Founder Neil Kumar, Ph.D.

This is BridgeBio’s second NDA acceptance following the acceptance of its NDA for fosdenopterin in molybdenum cofactor deficiency (MoCD) Type A in September 2020.

About Infigratinib

Infigratinib is an orally administered, ATP-competitive, FGFR1-3 tyrosine kinase inhibitor in development for the treatment of individuals with FGFR-driven conditions, including cholangiocarcinoma (bile duct cancer), urothelial carcinoma (bladder cancer) and achondroplasia, a bone growth condition in children.