On June 21, 2024 HUTCHMED (China) Limited ("HUTCHMED") reported that its partner Takeda has received notification from the European Commission ("EC") that it has approved FRUZAQLA (fruquintinib) as a monotherapy indicated for the treatment of adult patients with metastatic colorectal cancer ("CRC") who have been previously treated with available standard therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents, and who have progressed on or are intolerant to treatment with either trifluridine-tipiracil or regorafenib (Press release, Hutchison China MediTech, JUN 21, 2024, View Source [SID1234644480]).

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"With fruquintinib being the first and only selective inhibitor of all three VEGFRs to be approved in the EU for colorectal cancer, this decision represents a significant milestone in European oncology," added Josep Tabernero, MD, PhD, director of Vall d´Hebron Institute of Oncology (VHIO). "There is a clear need in Europe for patients and their clinicians to be able to access a new treatment option for previously treated metastatic colorectal cancer, and we are excited that this important step has been taken so that we can begin prescribing this new and differentiated medicine."

"We are delighted to have achieved EC approval for FRUZAQLA and that we can now offer a new therapeutic option for patients with previously treated metastatic colorectal cancer, regardless of their biomarker status," said Teresa Bitetti, President of the Global Oncology Business Unit at Takeda. "Patients in Europe with metastatic colorectal cancer have long needed additional treatment options, and we are grateful to be able to meet that need thanks to our partnership with HUTCHMED."

"This is a significant milestone for HUTCHMED, as it is the first product from our research and discovery engine to be approved in Europe, achieved through our partnership with Takeda to make this possible in such a short period of time," added Weiguo Su, PhD, Chief Executive Officer and Chief Scientific Officer of HUTCHMED. "This novel oncology medicine is currently improving the treatment outlook in the U.S. and China, and we look forward to seeing its impact for patients across Europe."

The EC’s approval has been granted following a positive opinion from the Committee for Medicinal Products for Human Use ("CHMP") in April 2024. The CHMP’s opinion was primarily based on results from the Phase III multiregional FRESCO-2 trial, which supported the Marketing Authorisation Application ("MAA") that was validated and accepted for review in June 2023. Data from FRESCO-2 were published in The Lancet in June 2023.

About CRC
CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer/World Health Organization, CRC is the third most prevalent cancer worldwide, associated with more than 1.9 million new cases and 900,000 deaths in 2022. In Europe, CRC was the second most common cancer in 2022, with approximately 538,000 new cases and 248,000 deaths.[1],[2] In the U.S., it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2024.[3] In Japan, CRC was the most common cancer, with an estimated 146,000 new cases and 60,000 deaths, in 2022.[2] Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.[4],[5],[6],[7],[8]

About the Phase III FRESCO-2 Trial
FRESCO-2 is a multiregional clinical trial conducted in the U.S., Europe, Japan and Australia investigating fruquintinib plus best supportive care ("BSC") versus placebo plus BSC in patients with previously treated metastatic CRC (NCT04322539). FRESCO-2 met all of its primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS), with consistent benefit among patients treated with fruquintinib, regardless of the prior types of therapies they received. Fruquintinib demonstrated a manageable safety profile in FRESCO-2, consistent with previously reported fruquintinib monotherapy studies. Adverse reactions leading to treatment discontinuation occurred in 20% of patients treated with fruquintinib plus BSC versus 21% of those treated with placebo plus BSC. Results from the study were presented at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) in September 2022 and subsequently published in The Lancet in June 2023.[9],[10]

About Fruquintinib
Fruquintinib is a selective oral inhibitor of all three VEG receptors (VEGFR‑1, ‑2 and ‑3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off‑target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for its potential use as part of a combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combinations with other anti‑cancer therapies.

About Fruquintinib Approval in China
Fruquintinib is approved for marketing in China, where it is co‑marketed by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. The approval was based on data from the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic colorectal cancer in China, which were published in The Journal of the American Medical Association, JAMA. Since its launch in China and as of mid‑2023, more than 80,000 patients with colorectal cancer have been treated with fruquintinib.

On June 21, 2024 Bristol Myers Squibb reported that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for KRAZATI (adagrasib) in combination with cetuximab as a targeted treatment option for adult patients with KRASG12C -mutated locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy (Press release, Bristol-Myers Squibb, JUN 21, 2024, View Source [SID1234644479]). This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR) results. Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial.

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"CRC with a KRASG12C mutation occurs in approximately 3-4% of CRC patients and has historically been challenging to treat,"2 said Rona Yaeger, MD, Gastrointestinal Oncologist & Early Drug Development Specialist, Memorial Sloan Kettering Cancer Center. "The FDA approval of KRAZATI combined with cetuximab now provides a new treatment option to these patients when their tumors do not respond well to prior therapies."

The approval is based on results from cohorts of the Phase 1/2 KRYSTAL-1 open-label study which evaluated KRAZATI (600 mg tablets administered orally twice daily) in combination with cetuximab in 94 patients with heavily pretreated CRC harboring a KRASG12C mutation. The study met its primary endpoint, with a confirmed ORR of 34% (n=94, 95% CI: 25-45) for KRAZATI with cetuximab, all of which were partial responses. The median DOR, one of the secondary endpoints, was 5.8 months (95% CI: 4.2-7.6).1 Current late-line standard of care options result in limited response rates (ORR 1-6%) after progression on chemotherapy ± VEGF/VEGFR inhibitors.3,4

KRAZATI is associated with the following Warnings & Precautions: Gastrointestinal adverse reactions including diarrhea, nausea, and vomiting, QTc interval prolongation, hepatotoxicity, and interstitial lung disease (ILD)/pneumonitis.1 Please see Important Safety Information below.

"Today’s approval of KRAZATI in CRC is the second in the U.S. for this therapy and the first for BMS’ recently expanded oncology portfolio. This is an important milestone for BMS and the patients we serve as we deliver on our commitment to provide innovative medicines for cancer," said Wendy Short Bartie, senior vice president, U.S. Oncology and Hematology at Bristol Myers Squibb. "We are proud to make KRAZATI – the first KRASG12C inhibitor to be FDA approved beyond non-small cell lung cancer – available to CRC patients, and look forward to further evaluating KRAZATI through our ongoing development program."

In 2022, the FDA granted breakthrough therapy designation for KRAZATI in combination with cetuximab for patients with KRASG12C -mutated advanced CRC whose cancer has progressed following prior treatment with certain chemotherapy and an anti-VEGF therapy.

KRAZATI is an irreversible inhibitor of KRASG12C with a long half-life (23 hours), dose-dependent pharmacokinetics (PK), and central nervous system (CNS) penetration, which, in combination with cetuximab may enhance inhibition of KRAS-dependent signaling or overcome adaptive feedback.

The company partnered with QIAGEN to develop a tissue-based companion diagnostic (CDx) for KRAZATI that is now available.

KRAZATI is a registered trademark of Mirati Therapeutics, Inc., a Bristol Myers Squibb company.

About KRYSTAL-1

KRYSTAL-1 is an open-label, multicenter, multiple expansion cohort Phase 1/2 trial to determine the safety and efficacy of KRAZATI in patients with advanced colorectal cancer (CRC) that harbor a KRASG12C mutation. The primary endpoint for the Phase 2 cohort of the KRYSTAL-1 study was objective response rate (ORR). Secondary endpoints included duration of response (DOR).

The KRYSTAL-1 study was funded by Mirati Therapeutics, Inc., a Bristol Myers Squibb company.

Select Safety Profile from KRYSTAL-1

The safety profile for KRAZATI plus cetuximab was evaluated in patients with KRASG12C -mutated, locally advanced or metastatic CRC, and is consistent with previous reports and known safety profile of each drug individually. Serious adverse reactions occurred in 30% of 94 patients who received KRAZATI in combination with cetuximab. The most common adverse reactions (≥20%) were rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, dizziness, cough, constipation, and peripheral neuropathy.1

About Colorectal Cancer

Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive, or gastrointestinal, system.5 CRC is the third most commonly diagnosed cancer in the world.6 In 2024, it is estimated that there will be approximately 106,590 new cases of the disease in the U.S.; it is the second leading cause of cancer-related deaths in the U.S. among men and women combined.7

KRAS is the most frequently mutated oncogene in human cancer and is one that drives oncogenesis in up to 50% of patients with CRC.2 The KRASG12C mutation occurs in approximately 3-4% of CRC cases.2

About KRAZATI (adagrasib)

KRAZATI (adagrasib) is a highly selective and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12 C-mutated cancers, as the KRASG12C protein regenerates every 24-48 hours.8 KRASG12C mutations act as oncogenic drivers and occur in approximately 14% of non-small cell lung cancer (NSCLC; adenocarcinoma) and 3% of several other cancers.9,10

In 2022, KRAZATI was granted accelerated approval for treatment of adult patients with KRASG12C -mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial.

KRAZATI continues to be evaluated as a monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C -mutated solid tumors, including NSCLC and CRC.

Please see U.S. Full Prescribing Information for KRAZATI.

INDICATIONS

KRAZATI in combination with cetuximab is indicated for the treatment of adult patients with KRASG12C -mutated locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

KRAZATI, as a single agent, is indicated for the treatment of adult patients with KRASG12C -mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

These indications are approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of a clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Gastrointestinal Adverse Reactions

KRAZATI can cause severe gastrointestinal adverse reactions.
Monitor and manage patients using supportive care, including antidiarrheals, antiemetics, or fluid replacement, as indicated. Withhold, reduce the dose, or permanently discontinue KRAZATI based on severity.
QTc Interval Prolongation

KRAZATI can cause QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (eg, torsades de pointes) or sudden death.
Avoid concomitant use of KRAZATI with other products with a known potential to prolong the QTc interval. Avoid use of KRAZATI in patients with congenital long QT syndrome and in patients with concurrent QTc prolongation.
Monitor ECGs and electrolytes, particularly potassium and magnesium, prior to starting KRAZATI, during concomitant use, and as clinically indicated in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, and in patients who are unable to avoid concomitant medications that are known to prolong the QT interval. Correct electrolyte abnormalities. Withhold, reduce the dose, or permanently discontinue KRAZATI, depending on severity.
Hepatotoxicity

KRAZATI can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
Monitor liver laboratory tests (AST, ALT, alkaline phosphatase, and total bilirubin) prior to the start of KRAZATI, and monthly for 3 months or as clinically indicated, with more frequent testing in patients who develop transaminase elevations. Reduce the dose, withhold, or permanently discontinue KRAZATI based on severity.
Interstitial Lung Disease/Pneumonitis

KRAZATI can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal.
Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever) during treatment with KRAZATI. Withhold KRAZATI in patients with suspected ILD/pneumonitis and permanently discontinue KRAZATI if no other potential causes of ILD/pneumonitis are identified.
ADVERSE REACTIONS

Serious adverse reactions occurred in 57% of 116 patients who received adagrasib in NSCLC patients. The most common adverse reactions in NSCLC patients (≥20%) were diarrhea, nausea, fatigue, vomiting, musculoskeletal pain, hepatotoxicity, renal impairment, dyspnea, edema, decreased appetite, cough, pneumonia, dizziness, constipation, abdominal pain, and QTc interval prolongation.
Serious adverse reactions occurred in 30% of 94 patients who received adagrasib in combination with cetuximab. The most common adverse reactions in CRC patients (≥20%) were rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, dizziness, cough, constipation, and peripheral neuropathy.
DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid concomitant use.
Strong CYP3A4 Inhibitors: Avoid concomitant use until adagrasib concentrations have reached steady state (after ~8 days).
Sensitive CYP3A4 Substrates: Avoid concomitant use with sensitive CYP3A4 substrates.
Sensitive CYP2C9 or CYP2D6 Substrates or P-gp Substrates: Avoid concomitant use with sensitive CYP2C9 or CYP2D6 substrates or P-gp substrates where minimal concentration changes may lead to serious adverse reactions.
Drugs That Prolong QT Interval: Avoid concomitant use with KRAZATI.
Please see Drug Interactions Section of the Full Prescribing Information for additional information.

USE IN SPECIFIC POPULATIONS

Females and Males of Reproductive Potential

Infertility: Based on findings from animal studies, KRAZATI may impair fertility in females and males of reproductive potential.
Lactation

Advise not to breastfeed.
Please see U.S. Full Prescribing Information for KRAZATI

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.

Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

On June 21, 2024 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported it presented new preclinical data from its investigational BCL6 PROTAC degrader ARV-393 at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Annual Congress that took place June 13-16, 2024 in Madrid, Spain, and presented new preclinical data from its PROTAC LRRK2 degrader program at the Biennial International LRRK2 Meeting that took place June 18-21, 2024 in Crete, Greece (Press release, Arvinas, JUN 21, 2024, View Source [SID1234644478]).

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Data presented at EHA (Free EHA Whitepaper) showed anti-tumor activity for the company’s investigational PROTAC BCL6 degrader, ARV-393, in preclinical models of B-cell lymphoma. In these preclinical models, ARV-393 potently and rapidly degraded the BCL6 protein and inhibited cell growth in diffuse large B-cell lymphoma (DLBCL) and Burkitt cell lines. ARV-393 showed tumor growth inhibition, including tumor regression, in various DLBCL cell line-derived xenograft (CDX) models and in multiple patient-derived xenograft (PDX) models of non-Hodgkin lymphoma (NHL), including germinal center B-cell-like (GCB), activated B-cell (ABC), GCB/ABC, BCL not otherwise specified (BCL/NOS) subtypes of DLBCL, and Burkitt lymphoma.

"These new preclinical data for ARV-393 demonstrate that in these models it can effectively target and induce the degradation of the BCL6 protein that is commonly deregulated in DLBCL," said John Houston, Ph.D., Chairperson, President, and Chief Executive Officer at Arvinas. "These encouraging results suggest that ARV-393 could be developed into a potential new treatment for patients with certain types of non-Hodgkin lymphoma, particularly those who have not responded to other treatments."

Preclinical data presented at the Biennial LRRK2 Meeting highlighted the potential of the company’s oral PROTAC LRRK2 degraders to treat neurodegenerative diseases. Preclinical studies in mice demonstrated full target engagement of LRRK2 kinase inhibitor and near-complete LRRK2 degradation with PROTAC LRRK2 degraders, but substantially less Type II pneumocyte enlargement compared to an experimental LRRK2 kinase inhibitor. In addition, the more noticeable Type II pneumocyte enlargement phenotype observed with the experimental LRRK2 kinase inhibitor was substantiated by the accumulation of surfactant protein C in lung, which was not observed after treatment with a PROTAC LRRK2 degrader.

"Nonclinical findings presented this week suggest the potential for a wide therapeutic index and manageable safety profile for PROTAC degraders versus experimental LRRK2 kinase inhibitors," said Angela Cacace, Ph.D., Chief Scientific Officer at Arvinas. "In earlier preclinical studies, Arvinas’ PROTAC LRRK2 degraders have been shown to cross the blood-brain barrier and degrade LRRK2, a large multidomain scaffolding kinase, in deep brain regions."

Arvinas’ oral PROTAC BCL6 degrader ARV-393 is currently in a phase 1 clinical trial in patients with NHL, and Arvinas also has an oral PROTAC LRRK2 degrader, ARV-102, currently being investigated in a phase 1 clinical trial in healthy volunteers.

About ARV-393

ARV-393 is an investigational PROTAC designed to degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. The BCL6 protein 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 has the potential to address the traditional undruggable nature of BCL6. ARV-393 is currently in a phase 1 clinical trial in patients with non-Hodgkin lymphoma.

About ARV-102

ARV-102 is an investigational PROTAC designed to degrade Leucine-rich repeat kinase 2 (LRRK2) which is a large multidomain scaffolding kinase. Human genetics, increased activity and expressions of LRRK2 is genetically involved in the pathogenesis of neurological diseases including Parkinson’s Disease and progressive supranuclear palsy. Arvinas is developing oral, blood-brain-barrier penetrant PROTAC degraders of LRRK2.

On June 20, 2024 CellxLife reported that Eric von Hofe, Ph.D., will serve as the company’s first Chief Executive Officer (Press release, CellXLife, JUN 20, 2024, View Source [SID1234644470])There are currently very few treatment options for children suffering from metastatic Ewing sarcoma or osteosarcoma. The most common treatment is surgical removal of the tumors in combination with radiation and chemotherapy. For children with recurring metastatic Ewing sarcoma or osteosarcoma, the 5-year survival rate is usually 20-30% and in the U.S., approximately $750,000 is spent on treatment over the course of a patient’s life. i,ii

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"Ewing sarcoma and osteosarcoma are devastating diseases that have far-reaching impact, particularly in pediatric patients and their caregivers," said Dr. von Hofe. "I am honored to join the CellxLife team to help advance efforts in bringing this promising new biotherapeutic to the thousands of children and families fighting these cancers globally."

Through CellxLife’s proprietary platform, dendritic cells are taken from the body and presented with the patient’s own tumor cell antigens, then re-administered back into the body as an immunotherapeutic vaccine to educate the immune system. Study data generated to date has indicated that this both activates immune cells to attack remaining cancer cells in the body and shapes the immunological memory to greatly reduce the chances of cancer recurrence. In a prior Phase 1 study, 75% of pediatric participants diagnosed with metastatic Ewing’s or osteosarcoma, who responded well to surgery, overcame their cancer, and are still alive today. Out of all the participants in the trial, 62.5% of children with metastatic osteosarcoma who were treated with the dendritic cell-based therapy lived for more than 15 years.

The CellxLife clinical team believes the therapy can cross over to other solid tumors, such as ovarian, breast, colorectal, pancreatic, glioblastoma, lung, and other solid tumors. The principle is the same; once a tumor is removed, the vaccine will shape the immunological memory of the cancer cells in the lymph nodes and greatly reduce the chances of cancer recurrence.

"This could be a breakthrough for anyone who is faced with the horrible realization that cancer could reoccur after their tumor is removed," said Ruvin Orbach, founder of CellxLife. "It’s an honor to have Eric on board as CEO at this important time of growth for CellxLife. We are committed to building the team and raising the capital required to further advance this de-risked therapeutic candidate. We are currently planning the Phase II trials with an orphan designation and significantly reducing the regulatory pathway for this promising immunotherapy."

Dr. von Hofe has over 30 years of experience in managing and overseeing biotechnology programs, with a focus on cancer immunotherapy and technology development. Most recently he led development efforts at AffyImmune Therapeutics where he oversaw the clinical development and orphan designation for a novel CAR-T cell therapeutic targeting refractory thyroid cancer. Previously, he was at Antigen Express where he led the development of an immunotherapeutic vaccine for breast and prostate cancer, resulting in a collaboration with Merck. Prior to that, he worked at Millennium Pharmaceuticals first as Program Director for Target Validation and later as Director of Programs & Operations, Discovery Research. Previously, Dr. von Hofe was Director, New Targets at Hybridon, Inc., where he coordinated in-house and collaborative research that validated gene targets for novel antisense medicines. Dr. von Hofe also held the position of Assistant Professor of Pharmacology at the University of Massachusetts Medical School, where he received a National Cancer Institute Career Development Award for defining mechanisms by which alkylating carcinogens create cancers. He received his Ph.D. in Experimental Pathology from the University of Southern California and was a postdoctoral fellow at both the University of Zurich and Harvard University School of Public Health.. The company was formed in late 2023 to advance a dendritic cell-based therapeutic vaccine candidate that aims to expand treatment options for children with recurring metastatic Ewing sarcoma and osteosarcoma.

On June 20, 2024 Yellowstone Biosciences ("Yellowstone" or "the Company"), a pioneer of soluble bispecific T-cell receptor (TCR)-based therapies for human leukocyte antigen (HLA) Class II (HLA-II) targets in oncology, reported to unlock a new class of therapeutically targetable, frequently expressed antigens with potential to significantly transform patient lives (Press release, Yellowstone Bioscience, JUN 20, 2024, View Source [SID1234644469]). Syncona Limited ("Syncona") committed £16.5 million to fund the Company in progressing its operational build, lead programme in acute myeloid leukaemia (AML), and exploration into expanding its pipeline.

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Spun out of the University of Oxford with the support of Oxford University Innovation (OUI), Yellowstone is built around the pioneering research of Professor Paresh Vyas, a world-renowned scientific academic, key opinion leader and practising clinician with a specialist focus on AML. Over 20 years, Prof. Vyas’ laboratory has collected a proprietary biobank of over 10,000 samples from over 3,000 AML patients, including a rare cohort of patients cured by allogeneic blood cell transplantation. From this cohort a novel set of frequently expressed peptide antigens presented by HLA Class II were identified, which could unlock a new class of highly selective cancer therapeutics.

With privileged access to this biobank, Yellowstone has been formed to develop soluble bispecific TCR-based therapeutics targeting HLA Class II presented peptides on the surface of cancer cells in a number of cancers with high unmet need. By targeting peptides presented by HLA-II molecules, the Company’s bispecific T-cell engagers have the potential to selectively kill target tumour cells, whilst sparing healthy cells. The Company will focus initially on its lead programme in AML, which accounts for 62% of all leukaemia deaths1 and where there is no universally agreed standard of care for the majority of patients. Beyond AML, Yellowstone’s technology also has the potential to extend life and change the treatment landscape in other common solid tumours that express HLA-II, including ovarian cancer, non-small cell lung cancer (NSCLC), colorectal cancer, prostate cancer, breast cancer, renal cancer and melanoma.

Yellowstone will be led by a world-class management team, including Prof. Vyas, as Co-founder and Chief Scientific Officer, and Julian Hirst, who joins as Co-founder and Chief Financial Officer, bringing with him 20 years’ experience in biotechnology and investment banking, including senior finance roles at Immunocore and MiroBio. Neil Johnston also joins as Executive Chair, having spent 17 years at Novartis, most recently as Global Head of Business Development and Licensing. The Company will be guided by Syncona, a leading FTSE 250 life sciences investor, who has supported company launch and will continue to shape Yellowstone’s operational build. Chris Hollowood, CEO of Syncona, and Gonzalo Garcia, Investment Partner at Syncona, will hold Board positions at Yellowstone as part of the lead investor’s ongoing involvement.

Professor Paresh Vyas, Co-founder and Chief Scientific Officer of Yellowstone, said: "Frequently expressed antigens that can be targeted therapeutically are notoriously difficult to find but, through two decades of research, we have identified a new class of targets that have potential to treat cancer and extend patient’s lives. We believe that our technology has the potential to selectively kill tumour cells, whilst sparing healthy cells, in a range of cancers. The strategy that we have built, alongside Syncona, will initially focus on developing highly selective TCR-based therapies for AML, where we have formidable experience and data. Beyond that, we are committed to broadening our pipeline to other cancer settings to maximise Yellowstone’s potential."

Gonzalo Garcia, Investment Partner at Syncona and Non-executive Director at Yellowstone, commented: "Yellowstone is the latest company formed from Syncona’s model of creating and building businesses based on exceptional science and world-class founders. The work Prof. Vyas has undertaken in this field is truly remarkable. Although difficult to identify, tumour-selective, frequently expressed antigens are particularly strong cancer targets as they allow development and manufacturing of therapies that can treat large numbers of patients. We believe that Syncona can build a globally leading UK company around this novel discovery that has significant patient and commercial potential."

Yellowstone’s academic founders received support during the spin out from OUI’s Dr. Susan Campbell and Dr. Benedicte Menn. As part of their ongoing involvement, OUI will hold a board observer position at the company.

Dr Benedicte Menn, Senior Investment Manager, Oxford University Innovation, said: "With ambition to become a world class UK company, Yellowstone is our latest spinout from the University of Oxford. The company has potential to treat and extend the life of patients with different forms of cancer, starting with acute myeloid leukaemia. We’re delighted that Yellowstone and Syncona are partnering on this launch and look forward to tracking the progress of the pipeline."