On July 28 Vicinitas Therapeutics, a biotechnology company advancing a proprietary targeted protein stabilization platform to develop novel therapeutics in cancer and genetic disorders, reported that launched with $65 million in Series A financing (Press release, Vicinitas Therapeutics, JUL 28, 2022, View Source [SID1234617106]). The financing was co-led by a16z and Deerfield Management, with participation from Droia Ventures, GV, The Mark Foundation for Cancer Research and the Berkeley Catalyst Fund. Vicinitas Therapeutics is a spin-out company that resulted from the Deubiquitinase Targeting Chimera (DUBTAC) platform, which was developed through an academic-industry research collaboration between the Novartis Institutes for BioMedical Research and researchers at the University of California, Berkeley.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Many diseases, including cancer and monogenic diseases, are often caused by specific proteins that are abnormally degraded and lost from the cell. In cancer, protective tumor suppressors are aberrantly destroyed, allowing cancer cells to circumvent cell death, thus promoting unobstructed cell proliferation. In monogenic disorders, mutations in certain genes cause the resulting protein to become unstable and degraded, which leads to abnormally low levels of the particular protein and the disease pathology. To date, many aberrantly degraded proteins have been considered "undruggable" or intractable to drug discovery efforts, and patients with these diseases would greatly benefit from a therapeutic that stabilizes and restores the levels of these proteins, allowing normal function to be restored.

The DUBTAC platform was developed to therapeutically target these degraded proteins by removing ubiquitin chains (tags on proteins that signal the cell to degrade and eliminate the protein using the cell’s protein disposal system) from specific proteins to stop their degradation and stabilize their levels for therapeutic benefit. DUBTACs, developed through an academic-industry research collaboration between Professor Daniel Nomura, his research group at UC Berkeley and scientists at the Novartis Institutes for BioMedical Research, are bifunctional small molecules consisting of a protein-targeting ligand connected via a linker to a deubiquitinase (DUB) recruiter. In a unique application of induced-proximity biology, DUBTACs bring a DUB into the vicinity of a ubiquitin-tagged protein to remove the ubiquitin chain and subsequently prevent degradation of the target protein.

In a hallmark study published in Nature Chemical Biology, Dr. Nomura, the Nomura Lab and Novartis colleagues discovered covalent allosteric recruiters against OTUB1, a known DUB. They showed that this covalent OTUB1 recruiter could be linked to various protein-targeting ligands to stabilize the levels of aberrantly degraded proteins, including the mutated chloride channel CFTR that causes cystic fibrosis and the tumor suppressor WEE1 kinase in cancer cells.

Vicinitas Therapeutics has exclusively licensed the DUBTAC platform from both UC Berkeley and Novartis and aims to become the leading company in targeted protein stabilization by developing next-generation disease therapies against an entire class of previously inaccessible aberrantly degraded proteins. The company is initially focused on developing therapies in cancer and monogenic diseases.

"We are excited about the potential of the DUBTAC platform to develop novel therapies against therapeutic targets that were previously deemed undruggable and will respond to protein stabilization," said Daniel K. Nomura, Ph.D., founder of Vicinitas Therapeutics and Professor of Chemical Biology in the Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology at UC Berkeley.

"The concept of chemically induced proximity – using multispecific molecules to bring two targets physically together – has yielded notable successes in the field of protein degradation," said Jorge Conde, General Partner at a16z. "Vicinitas is leveraging its proprietary DUBTAC platform to pioneer the emerging space of targeted protein stabilization. This approach has the potential to access highly valued yet currently undruggable proteins and create differentiated therapies that will impact patient lives."

Leadership Team and Formation of Scientific Advisory Board

The Vicinitas Therapeutics team is comprised of scientific leaders from academia and industry who have demonstrated years of commitment and success in the field, and who remain dedicated to advancing science and technology and delivering highly impactful drugs.

Vicinitas Therapeutics’ leadership team includes:

Daniel K. Nomura, Ph.D., Founder and Professor of Chemical Biology in the Departments of Chemistry, Molecular and Cell Biology and the Molecular Therapeutics Division, and Nutritional Sciences and Toxicology, UC Berkeley; Investigator at the Innovative Genomics Institute
Daniel Marquess, D.Phil, Chief Scientific Officer
Joe Budman, Ph.D., Vice President of Biology
Vicinitas Therapeutics’ board of directors includes:

Jorge Conde, General Partner, a16z
Cameron Wheeler, Ph.D., Partner, Deerfield Management
George Golumbeski, Ph.D., Partner, Droia Ventures
Daniel K. Nomura, Ph.D., Founder and Professor of Chemical Biology in the Departments of Chemistry, Molecular and Cell Biology and the Molecular Therapeutics Division, and Nutritional Sciences and Toxicology, UC Berkeley; Investigator at the Innovative Genomics Institute
Vicinitas has also established a scientific advisory board, including:

Daniel K. Nomura, Ph.D., Founder and Professor of Chemical Biology in the Departments of Chemistry, Molecular and Cell Biology and the Molecular Therapeutics Division, and Nutritional Sciences and Toxicology, UC Berkeley; Investigator at the Innovative Genomics Institute
Michael Rape, Ph.D., Professor, Department of Molecular and Cell Biology, UC Berkeley; Investigator of the Howard Hughes Medical Institute
Thomas Maimone, Ph.D., Associate Professor in the Department of Chemistry, UC Berkeley
James Olzmann, Ph.D., Associate Professor, Departments of Molecular and Cell Biology and Nutritional Sciences and Toxicology, UC Berkeley; Investigator of the Chan Zuckerberg Biohub
Kevan Shokat, Ph.D., Professor, Department of Cellular and Molecular Pharmacology, UCSF; Investigator of the Howard Hughes Medical Institute
F. Dean Toste, Ph.D., Gerald E. K. Branch Distinguished Professor of Chemistry, UC Berkeley
Angela Koehler, Ph.D., Associate Professor, Biological Engineering, MIT, Associate Director, Koch Institute for Integrative Cancer Research at MIT
"Vicinitas Therapeutics has emerged as a pioneer of targeted protein stabilization, and we’re excited to be a part of the Series A funding," said Cameron Wheeler, Ph.D., Partner at Deerfield Management. "As a therapeutic modality, stabilization has the power to elicit substantial changes to disease biology with relatively minor alterations to target proteins, and we are optimistic about the potential of the DUBTAC platform across oncology, rare and chronic diseases."

On July 28, 2022 Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer, reported that it will report its second quarter 2022 financial results on Thursday, August 4, 2022 (Press release, Deciphera Pharmaceuticals, JUL 28, 2022, View Source [SID1234617058]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In connection with the earnings release, Deciphera’s management team will host a live conference call and webcast at 8:00 AM ET on Thursday, August 4, 2022, to discuss the Company’s financial results and provide a corporate update.

The conference call may be accessed via this link: https://register.vevent.com/register/BI14cfe386c5004efcba5c94f8783e2435.

A live webcast of the conference call will be available in the "Events and Presentations" page in the "Investors" section of the Company’s website at View Source A replay will be available on the Company’s website approximately two hours after the conference call and will be available for 30 days following the call.

On July 28, 2022 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on the development of GLSI-100, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery, reported the following (Press release, Greenwich LifeSciences, JUL 28, 2022, View Source [SID1234617075]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

We believe that the Company is well capitalized with cash balance reported on the Company’s Form 10-Q for the period ending March 31, 2022 of $19.7 million
Current burn rate has been low due to virtual corporate structure and outsourcing strategy
Commencement of Phase III clinical trial, Flamingo-01, is expected to increase burn rate gradually over time as more sites are activated, patient treatment begins, and commercial manufacturing commences
Recent "at the market" (ATM) sale agreement (see description below) entered into on July 12, 2022 with one of the leading biotech investment banks is a flexible financing vehicle designed to be used over time at share prices and quantities of shares at our sole discretion
We intend to use the ATM facility opportunistically in the future and do not presently intend to use the full amount of the ATM facility
We believe that strategic use of the ATM facility could begin our transition to an investment banking syndicate and to fundamental biotech institutional investors to complement the current retail investor base
An update on the Flamingo-01 trial is expected to be provided shortly
An update on the transition from the published Phase IIb data to future publications of open label Phase III data is expected to be provided shortly
About At the Market Sales Agreement

As disclosed in the Prospectus Supplement dated July 12, 2022, an ATM offering may be made from time to time through the investment bank by selling Company stock at the best available market price over time without a price discount and without warrants or additional dilutive financial structure. The number of shares that are sold will fluctuate based on the market price and demand for the Company’s common stock, and any additional conditions set by the Company. It is not possible at this stage to predict the number of shares that will be sold or the gross proceeds to be raised in connection with those sales. There can be no assurance that the Company will sell any shares under or fully utilize this source of financing.

More specifically, each time the Company wishes to issue and sell shares of the Company’s common stock under the sales agreement, the Company will notify the investment bank of the number of shares to be issued, the dates on which such sales are anticipated to be made, any limitation on the number of shares to be sold in any one day and any minimum price below which sales may not be made. The investment bank will use its commercially reasonable efforts consistent with its normal trading and sales practices to sell such shares up to the amount specified on such terms on the open market or in block trades.

The Company currently intends to use the net proceeds from this offering for general corporate purposes, which may include, but are not limited to, funding the clinical development and manufacturing and other expenses for GP2, research and development, general and administrative expenses, license or technology acquisitions, and working capital and capital expenditures. The Company may also use a portion of the remaining net proceeds, if any, to acquire or invest in complementary businesses, products and technologies, although there are no current commitments or agreements with respect to any acquisitions as of the date hereof.

About FLAMINGO-01 and GLSI-100

FLAMINGO-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2/neu positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial will be led by Baylor College of Medicine and will include US and international clinical sites from university-based hospitals and cooperative networks. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients will be randomized to GLSI-100 or placebo, and up to 100 patients of other HLA types will be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater. The trial is currently registered on clinicaltrials.gov and can be seen here. For future updates about FLAMINGO-01 please visit the Company’s clinical trial tab at View Source

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 282,000 new breast cancer patients and 3.8 million breast cancer survivors in 2021. HER2/neu (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

On July 28, 2022 Tallac Therapeutics, Inc., a privately held biopharmaceutical company harnessing the power of innate and adaptive immunity to fight cancer, reported that the first patient has been dosed with TAC-001 in a Phase 1/2 clinical trial for patients with advanced or metastatic solid tumors (Press release, Tallac Therapeutics, JUL 28, 2022, View Source [SID1234617091]). TAC-001 is the company’s lead clinical candidate from its novel Toll-like Receptor Agonist Antibody Conjugate (TRAAC) platform and the first to enter the clinic.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The initiation of the first-in-human study for our lead therapeutic candidate represents a major milestone for Tallac as we work to advance our differentiated pipeline of immunotherapy candidates derived from our TRAAC platform," said Hong I. Wan, Ph.D., president, CEO and co-founder of Tallac Therapeutics. "As this study advances, we are also progressing additional assets in our pipeline and plan to file an investigational new drug application (IND) in the beginning of next year for our Phase 1 study in partnership with ALX Oncology Holdings Inc. (Nasdaq: ALXO) for ALTA-002. This therapeutic candidate is a systemically delivered toll-like receptor 9 (TLR9) agonist targeting dendritic cells via SIRP-alpha receptors."

The Phase 1/2 trial, known as INCLINE-101 (NCT05399654), is an open label, multicenter, dose escalation and expansion study of TAC-001 in patients with select advanced or metastatic solid tumors. It is designed to evaluate the safety, pharmacokinetics and preliminary anti-tumor activity of TAC-001 administered intravenously.

"TAC-001 is unique in that it integrates B cells and TLR9 activation to trigger innate and adaptive anti-tumor immune responses, and in preclinical studies demonstrated potent single-agent activity," said Candy Bermingham, Ph.D., vice president, clinical science at Tallac Therapeutics. "We look forward to better understanding the clinical utility of TAC-001 in advanced solid tumors and the potential of this molecule to address the high unmet treatment needs that remain in multiple cancer types."

Toll-like receptor 9 (TLR9) agonists are a class of immunotherapy that generate both innate and adaptive immune response, which may produce more robust and durable anti-cancer immunity to help overcome resistance to standard-of-care oncology treatments. TLR9 agonists have demonstrated clinical activity in melanoma patients when administered intratumorally. B cells express TLR9 and play pivotal roles in the immune system, and represent a major component of the tumor microenvironment, where they are predominantly associated with tertiary lymphoid structure (TLS). The presence of B cells and TLS is a positive prognostic factor and predicts treatment response to checkpoint inhibitors in multiple solid tumor types.

Tallac Therapeutic’s TRAAC platform is designed to deliver a potent and differentiated TLR9 agonist (T-CpG) for targeted immune activation via systemic administration. TAC-001 is an antibody-oligonucleotide conjugate, comprised of T-CpG conjugated to an antibody against CD22, a receptor restricted to B cells, including tumor-infiltrating B cells. Preclinical studies demonstrate that the innate and adaptive immune responses triggered by TAC-001 leads to robust, curative, and durable single agent anti-tumor activity in checkpoint inhibitor resistant and refractory tumor models. Increased B cell infiltration, T cell effector functions and modulation of suppressive myeloid cells within the tumor microenvironment were observed following systemic TAC-001 administration. These results support the development of TAC-001 for a broad range of solid tumor malignancies, particularly in the tumor types with B cell/TLS involvement.

About TAC-001
TAC-001 is a Toll-like Receptor Agonist Antibody Conjugate (TRAAC) comprised of a potent toll-like receptor 9 agonist (T-CpG) conjugated to an antibody against CD22, a receptor restricted to B cells, including tumor-infiltrating B cells. TAC-001 is designed to systemically deliver T-CpG to B cells by binding to CD22, leading to internalization of TAC-001, TLR9 signaling, B cell activation and a cascade of immune reactions. Preclinical studies demonstrate that the innate and adaptive immune responses triggered by TAC-001 leads to potent anti-tumor activity. TAC-001 is being developed for the potential treatment of solid tumors.

On July 28, 2022 Novartis and the University of California, Berkeley reported that they have extended their research-based collaboration to develop new technologies for the discovery of next-generation therapeutics, following its successes over the last five years (Press release, Novartis, JUL 28, 2022, View Source [SID1234617107]). The combined research team is pursuing a vast number of disease targets in cancer and other illnesses that have eluded traditional small-molecule compounds and drug discovery strategies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"One of the biggest challenges facing drug discovery is that the majority of proteins are currently still considered ‘undruggable,’" said covalent chemoproteomics expert Daniel Nomura, Director of the Institute and Professor of Chemistry, Molecular and Cell Biology in the Molecular Therapeutics Division, and Nutritional Sciences and Toxicology at UC Berkeley. "Most proteins do not possess well-defined binding pockets or ‘ligandable hotspots’ that can be pharmacologically and functionally targeted for therapeutic benefit. Tackling these undruggable proteins requires the development of innovative technologies for ligand discovery and the discovery of novel therapeutic modalities to functionally manipulate these intractable proteins for therapeutic benefit."

This research collaboration allows UC Berkeley scientists to work with their scientific peers at Novartis Institutes for BioMedical Research (NIBR) to find new cures for debilitating illnesses. The second phase of the research collaboration is the Novartis-Berkeley Translational Chemical Biology Institute, and is based at UC Berkeley. The Berkeley team includes Professors Nomura, F. Dean Toste, Thomas Maimone, Ziyang Zhang, and James Olzmann. The science and strategy underpinning the research collaboration aim to harness covalency, coupled with chemoproteomics technology, to enable the discovery of small-molecule compounds that could ultimately form the basis of proximity-based therapeutics.

"I am thrilled to be able to help build off the momentum gained during the past five years and equally excited to synergize with new colleagues," said Maimone, Associate Professor of Chemistry at UC Berkeley. "With expanded scientific expertise, increasingly sophisticated chemistries, and new envisioned therapeutic modalities, the next several years will be exhilarating."

The inaugural research collaboration, the Novartis-Berkeley Center for Chemistry and Proteomics Technologies, led to multiple groundbreaking discoveries, including the development of several novel recruiters of E3 ubiquitin ligases that can be exploited in the degradation of disease causing proteins; the development of new chemistry that can be used to enhance the scope of covalent chemoproteomic technologies; and the creation of a new therapeutic platform called Deubiquitinase Targeting Chimeras (DUBTACs) for stabilizing the levels of proteins that are aberrantly degraded. This work has led to several publications and patents and facilitated the training of emerging scientists. The DUBTAC platform is also the basis of a spinout company, Vicinitas Therapeutics, focused on developing DUBTACs into a unique, potential, proximity-based therapeutic modality for cancer, genetic disorders, and other indications.

"We joined forces with Berkeley five years ago because we knew that many compelling targets in disease biology remain beyond reach – and that no one team or discipline could tackle the toughest among them alone," said Jay Bradner, President of NIBR. "Today, we recommit to working shoulder-to-shoulder to make these so-called ‘undruggable’ targets druggable."

Moving forward, the alliance will continue to develop new chemistries and chemical technologies for targeting undruggable proteins, expand upon emerging therapeutic modalities such as targeted protein degradation (TPD) that exploit the cell’s natural protein disposal system to destroy disease-causing proteins, and develop new therapeutic modalities that enable access into larger swaths of the undruggable protein landscape.