On October 14, 2020 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported platform updates and disclosed five additional programs from its preclinical pipeline (Press release, Arvinas, OCT 14, 2020, View Source [SID1234568465]). Arvinas’ portfolio encompasses a range of validated and undruggable targets in oncology, immuno-oncology, and neuroscience.

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"We continue to expand our pipeline and further our leadership position in targeted protein degradation by leveraging the PROTAC Discovery Engine, our integrated platform that we’ve been advancing since 2013," said John Houston, Ph.D., President and Chief Executive Officer of Arvinas. "With the programs introduced today, and the important breakthroughs we’ve made over the years – such as achieving oral bioavailability in human patients and successfully penetrating the blood-brain barrier in preclinical studies – we make it clear that we have the ability to rapidly progress Arvinas’ deep pipeline in order to benefit patients in multiple areas of high unmet need."

"The targets we announced today represent a mix of oncology, immuno-oncology and neuroscience programs," said Ian Taylor, Ph.D., Chief Scientific Officer of Arvinas. "Our progress with classic ‘undruggable’ targets like KRAS reinforces our commitment to finding solutions for patients and demonstrates the power of Arvinas’ PROTAC Discovery Engine in generating novel therapies."

In addition to progressing its platform and preclinical pipeline, Arvinas is testing two PROTAC protein degraders in human clinical trials: ARV-110 for the treatment of men with metastatic castrate-resistant prostate cancer and ARV-471 for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer. Arvinas plans to share updated data for these programs later in the fourth quarter of 2020.

Newly Announced Programs

BCL6 (Oncology)

B-cell lymphoma 6 protein (BCL6) is a transcriptional repressor implicated in B cell lymphomas and facilitates B cell tolerance of rapid proliferation and somatic gene recombination via repressing cell cycle checkpoints, terminal differentiation, apoptosis, and the DNA damage response. PROTAC-mediated degradation would address the scaffolding function of BCL6. Arvinas anticipates filing an IND for this program in 2022.
KRAS (Oncology)

Kirsten rat sarcoma (KRAS) is a classic "undruggable" target, due to its lack of deep "pockets," and is associated with poor prognosis and resistance to standards of care in several tumor types. Arvinas is developing pan-KRAS mutant and mutant-specific KRAS degraders, e.g., G12D and G12V. Arvinas anticipates filing an IND for this program in 2023.
Myc (Oncology)

Myelocytomatosis (Myc) proteins are implicated in up to 70% of all human cancers. Targeting Myc indirectly, such as by inhibiting transcription modulators, has not been successful, but PROTAC-mediated degradation has the potential to directly target and degrade Myc. This is an Exploratory-stage program.
HPK1 (Immuno-oncology)

Hematopoietic progenitor kinase 1 (HPK1) is a suppressor of T cell activation and targeting HPK1 can enhance anti-tumor immune responses. PROTAC-mediated degradation has the potential to address the proposed scaffolding component of HPK1’s activity. This is an Exploratory-stage program.
mHTT (Neuroscience)

Huntington’s disease is caused by a mutation in the huntingtin (HTT) gene. PROTAC degradation has the potential to allow the selective targeting of mutant HTT protein without impacting wild-type HTT protein. This is an Exploratory-stage program.

On October 14, 2020 Nimbus Therapeutics, a biotechnology company designing breakthrough medicines through structure-based drug discovery and development, reported the close of a $60 million private financing round from life science investors RA Capital Management and BVF Partners L.P. ("RA" and "BVF", respectively) (Press release, Nimbus Therapeutics, OCT 14, 2020, View Source [SID1234568464]). The funds support the acceleration of Nimbus’ Phase 1 allosteric tyrosine kinase 2 (TYK2) inhibitor into Phase 2 early next year, its hematopoietic progenitor kinase 1 (HPK1) inhibitor into the clinic next year, as well as the advancement of its preclinical portfolio of new medicines.

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"Today’s financing evidences the remarkable success of our structure-based drug discovery approach and the exciting data our pipeline has generated," said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. "This financing also defines a pathway for our future, and while we could not welcome all the investors with interest in Nimbus into this round, we expect with continued success to build on this financing by bringing on additional new investment in 2021."

"Nimbus’ compelling TYK2 clinical data clearly positions us for a Phase 2b trial, which will generate data on the same endpoints as BMS’ TYK2 program," said Bruce Booth, D.Phil., co-founder and Chairman of the Board of Nimbus. "We are fortunate to have RA and BVF join Nimbus, and we welcome Laura Stoppel from RA to the Board."

"We’re proud to join Nimbus’ circle of investors and to lead this most recent financing round," said Peter Kolchinsky, Ph.D., a founder and Managing Partner of RA Capital Management. "We see tremendous potential for Nimbus’ lead program, one of only two clinical allosteric approaches to TYK2 inhibition, and for the company’s newly added preclinical programs to address important therapeutic needs in oncology, immunology, and metabolism."

On October 14, 2020 NOXXON Pharma N.V. (Euronext Growth Paris: ALNOX), a biotechnology company focused on improving cancer treatments by targeting the tumor microenvironment (TME), reported that all three patients of the second dose cohort have been enrolled into the brain cancer clinical trial testing CXCL12 inhibitor, NOX-A12, and have already received the planned initial treatment (Press release, NOXXON, OCT 14, 2020, View Source [SID1234568428]). The Phase 1/2 clinical study investigates three dose regimens of NOX-A12 (200, 400 and 600 mg/week), each combined with external beam radiotherapy in newly diagnosed brain cancer patients.

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Once the last patient in the second cohort completes four weeks of therapy of NOX-A12 and radiotherapy, the independent Data Safety Monitoring Board (DSMB) will determine whether it is safe to proceed from the middle to the highest dose level of NOX-A12. The approved protocol plans for each patient to be treated with NOX-A12 for up to six months.

"The combination of NOX-A12, at both low and middle doses, and radiotherapy has been well tolerated by the patients participating in this clinical trial. Recruitment of the last cohort could start as early as November once the next safety analysis confirms benign safety profile of NOX-A12," said Dr. Frank Giordano, Chairman of the Department of Radiation Oncology at the University Hospital Bonn.

"Completing patient recruitment is an important step in the continued clinical assessment of this novel therapy for patients with difficult-to-treat and highly aggressive brain cancer. As a measure to ensure the timely completion of the study under the current challenging conditions posed by the COVID-19 pandemic, we will soon open additional clinical sites in Germany to increase recruitment capacity," commented Aram Mangasarian, CEO of NOXXON.

On October 13, 2020 BrodenBio Co., Ltd. reported the company has completed the pre-A round of financing of tens of millions (CNY), led by Tao Capital, followed by Lapam Capital and Tibet Ruihai Enterprise Management Center (L.P.) (Press release, BroadenBio, OCT 13, 2020, View Source [SID1234640197]).

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On October 13, 2020 Immuneel Therapeutics Private Limited (Immuneel) reported that it has entered into a multi-asset collaboration and licensing agreement with Hospital Clínic de Barcelona (HCB) and Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (Press release, Imuneel, OCT 13, 2020, View Source [SID1234618847]). Under the collaboration which opens up opportunities for co-development of advanced assets to be deployed in Spain and India, Immuneel acquired the exclusive rights to develop and commercialise autologous ARI-0001, a CD19 Chimeric antigen receptor (CAR) T cell therapy, in India.

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This agreement puts Immuneel as a front-runner in the pursuit of offering accessible and affordable CAR Ts to patients in India through registration clinical trials and its investments in further process optimization.

Speaking about this milestone collaboration:

Ms. Kiran Mazumdar Shaw (Co-founder, Immuneel) said, "This partnership with HCB & IDIBAPS is pathbreaking and heralds the advent of life saving CAR T therapy for patients in India. Immuneel is committed to providing affordable access to this cutting-edge therapy at state-of-the-art facilities housed at the Mazumdar Shaw Cancer Centre. I would particularly like to call out Dr. Campistol and Dr. Juan Uriach for their willingness to partner with us in our mission to give hope to cancer patients who can benefit from cell therapies."

HCB/IDIBAPS are public institutions that collaborated with a vision to create ARI-0001 as a product that can be an affordable option to treat patients with B cell malignancies in Spain. Dr. JM. Campistol (CEO, HCB) said, "We are extremely proud about this collaboration with Immuneel. We are convinced about the benefits of our CAR T therapy on patients with ALL. This is the beginning of a fruitful and promising collaboration between our academic research efforts (HCB & IDIBAPS) and Immuneel to improve the treatment of hematological disorders."

Dr. Elias Campo (Research Director, HCB-IDIBAPS) added, "CAR T based therapies have shown efficacy in the treatment of certain leukemias and lymphomas. With this partnership we will improve our knowledge on this kind of therapies and more patients will benefit from them".

Dr. Juan Uriach Torello (Scientific Business Advisor, Immuneel-HCB-IDIBAPS Collaboration) who has played a key advisory role in the partnership added, "This a remarkable display of alignment on affordable cell therapy between an academic hospital and a start-up; and also, a demonstration of hope for Spain and India."

ARI-0001 is a novel 2nd generation autologous CD19 CAR T, that has been extensively studied in-vitro and in-vivo. Clinical data from a recently concluded Phase 1-2 trial showed ARI-0001 to be a safe and efficacious product, with persistence of CAR T cells and response in patients who had failed previous therapies. ARI-0001 is currently under review for approval as a hospital exemption product by Spanish Drug Agency (AEMPS). "This collaboration and ARI-0001 licensing marks a strong foundation event on which Immuneel will bring its purpose to fruition – to enable really high quality and affordable cell therapy for patients in India. The collaboration seeks to align efforts to globalise affordable high-quality cell therapy strategies developed in India and Spain. We are really excited to be able to accelerate access to transformative therapies with ARI-0001 and build on the excellent data already generated in Spain" said Dr. Arun Anand, COO, Immuneel.

Dr. Siddhartha Mukherjee (Co-founder, Immuneel) further added, "Immuneel is extremely proud to bring this cutting-edge cell therapy to India. These "living drugs", created from genetically modified cells, have saved the lives of hundreds of cancer patients around the world but have been unavailable in India. Unlike standard medicines, these cell therapies have to be produced and delivered with immense care and technical finesse. A clinically tested target like CD 19 will enable Immuneel validate its clinical delivery for CAR T cells in India."

According to Dr. Kush M Parmar (Co-founder, Immuneel) "As Immuneel sets out on its mission to enable access to cellular therapies in India, CD19 CAR T as a first product reflects the thoughtful and stepwise approach being taken. The manufacturing, regulatory, clinical and delivery experience in bringing this validated approach to patients in India will lay the foundation for Immuneel’s leadership role in cellular therapies in the region and positions us well to build a pipeline of next-generation products for many patients in need."

"The agreement represents a first-rate opportunity to open the use of a product, that has been used only in our Hospital Clínic, for the patients of a continental-sized country like India, with a very different regulatory environment that can facilitate the validation of improvements that also could help our patients", says Dr. Manel Juan, head of the Immunology Department of Hospital Clínic and head of the Immunogenetics of the autoinflammatory response group at IDIBAPS. Dr. Álvaro Urbano, director of the Clínic Institute of Hemato-oncological Diseases and head of the IDIBAPS group on Hematopoietic progenitor cell transplantation, points out that, "we are very proud because the effort of a large team of the Hospital Clinic/IDIBAPS has made it possible that thanks to the ARI001 many patients in India will have access to a CART, which they could not otherwise afford. At the same time, it is a great responsibility to maintain the demands of quality and efficacy, as it is highly complex gene therapy. This will be the focus of the agreement that we have signed with Immuneel".

Additional terms were not disclosed.

About CD19 CAR T cell therapy

CD19 CAR T therapy is an adoptive autologous antitumor immunotherapy for patients with resistant or refractory CD19 + leukemia or lymphoma. This autologous product consists of a suspension of T-cells obtained from a patient, activated & genetically modified to express a chimeric antigen receptor (CAR) on its surface, in this case CD19. CAR Ts typically consist of a binding domain, a transmembrane domain & co- stimulatory molecules. Three CD19 CAR T products have been approved so far globally.