On September 12, 2022 Universal Diagnostics (Universal DX), a bioinformatics and multi-omics company on a mission to transform cancer into a curable disease, reported the results of a proof of principle study demonstrating that the analysis of microbiome signatures in plasma can assist in early detection of colorectal cancer (CRC) (Press release, Universal Diagnostics, SEP 12, 2022, View Source [SID1234619453]).

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!

This advancement follows the company’s promising early findings that revealed early-stage colorectal cancer detection through analysis of cell-free circulating tumor DNA (ctDNA) methylation, mutation and fragmentation patterns by using targeted sequencing analysis, advanced computational biology and machine learning algorithms to detect colorectal cancer and advanced adenomas.

"While methylation, mutation and fragmentation are still the core of early CRC detection, we think microbiome is an interesting addition to our proprietary technological platform Signal-X as we build out the platform," said Christian Hense, COO at Universal DX. "As we learn more about microorganisms and how they interact in communities within our bodies to change the way we feel and function, we hope this type of data analysis will help patients get access to earlier and more sensitive screening, individualized guidance for treatment, and advanced monitoring techniques."

Over the last two decades, microbiome has become a key focus in the nutrition field, giving clinicians and patients a window into how diet and gut bacteria plays into overall health. The data presented by Universal DX shows that microbiome research can have a profound impact on other areas of healthcare, such as oncology. This body of research from Universal DX is being used to build "Signal-X", a platform to detect multiple types of cancer. Its first product, "Signal-C", detects early-stage colorectal cancer and adenomatous polyps.

"The data are clear: by detecting cancer earlier, we can save more lives," said Dr. James Kinross, Consultant Surgeon at Imperial College London and co-author of the study. "While we have a way to go until we can catch all cancers in their earliest stages, we continue to make great and promising progress. The work Universal DX is doing on Signal-X is one example. Much less invasive than a colonoscopy, accurate liquid biopsies will likely increase screening rates, improve outcomes and save lives."

Study Conclusions:

Changes in gut microbiota have been shown to have a link into colorectal cancer development and progression.
Measuring cancer-related microbiome alterations in plasma cell-free DNA (cfDNA) could offer an accurate, non-invasive approach for early cancer detection, leading to decreased cancer mortality.
cfDNA analysis coupled with model building achieved high sensitivity, including at stage I/II and stage III/IV, at equally accurate specificity.
Universal DX leverages proprietary, state-of-the-art computational biology tools combined with targeted next generation sequencing (NGS) assay platform that allows for simultaneous detection of methylation and microbiome signals for highly-sensitive cancer signal scoring of cell-free DNA regions linked to cancer of interest.

Hense continued: "Colorectal cancer is the third deadliest cancer in the United States. When it is detected early, the 5-year survival rate increases from 60% to 90%. This staggering difference is something we can’t ignore. At Universal DX, we are committed to finding better detection methods that catch dangerous cancers as early as possible, so that we can save lives. Microbiome signatures are a promising avenue, but this is just the beginning."

The company presented it findings live at ESMO (Free ESMO Whitepaper) in Paris on September 11th; abstract 358P – Analysis of microbiome signatures in plasma for early CRC detection.

On September 12, 2022 Gamida Cell Ltd. (Nasdaq: GMDA), the leader in the development of NAM-enabled cell therapies for patients with hematologic and solid cancers and other serious diseases, reported the presentation of data supporting the potential of omidubicel for the treatment of patients with blood cancers in need of an allogeneic hematopoietic stem cell transplant at the 2022 Cord Blood Connect Meeting, being held in South Beach, Florida (Press release, Gamida Cell, SEP 12, 2022, View Source [SID1234619452]). "We continue to be encouraged by the growing body of evidence supporting the improved outcomes and lower infection rates seen in patients treated with omidubicel as well as the superior health-related quality of life scores compared to transplantation with UCB. We also demonstrated the potential role for omidubicel to address the unmet need for patients who are currently eligible for transplant, but cannot find a match," said Julian Adams, chief executive officer of Gamida Cell. "Our omidubicel BLA was accepted by the FDA and granted priority review with a PDUFA date of January 30, 2023, which we believe further underscores the unmet need for patients with blood cancers in need of a stem cell transplant."

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!

Gamida Cell presented a poster titled "Health-Related Quality of Life (HRQL) Following Transplantation with Omidubicel Versus Umbilical Cord Blood (UCB) in Patients with Hematological Malignancies: Results from a Phase III Randomized, Multicenter Study," which included an analysis of 75 patients to evaluate changes in HRQL measures between the two study arms. Outcomes evaluated included Functional Assessment of Cancer Therapy General (FACT-G) domain scores for physical, social/family, functional and emotional well-being, and EQ-5D-3L index scores at days 42, 100, 180 and 365 post-transplant. During the first-year post-transplant, patients receiving omidubicel had numerically superior average FACT-G domain and EQ-5D-3L index scores compared to UCB, with mean differences across time points ranging from 1.4-3.1 for physical well-being, 0-1.3 for social/family well-being, 0.5-1.4 for emotional well-being, 1.6-3.2 for functional well-being, and 0.03-0.09 for the EQ-5D-3L index score. The data suggest meaningfully greater preservation or improvement of important HRQL domains in patients treated with omidubicel compared to UCB. Learn more

Gamida Cell also presented a poster titled "Projected Impact of Omidubicel on Racial and Ethnic Disparities in Allogeneic Hematopoietic Cell Transplant Access and Outcomes for Patients with Hematologic Malignancies in the US," which featured an analysis of projected impact of allogeneic hematopoietic cell transplant (allo-HCT) access and clinical outcomes in a hypothetical population of 10,000 allo-HCT-eligible patients with hematologic malignancies lacking an HLA-matched related donor. Assuming 20% omidubicel use, the proportion of patients receiving allo-HCT increased by 71% in Black, 43% in Asian, 30% in Hispanic, and 5% in white patients. The model suggests that access to omidubicel, upon approval, is projected to decrease time to allo-HCT and improve patient outcomes, with the greatest improvements among the racial and ethnic groups underserved by the current standard of care. Learn more

In a poster titled "Hematopoietic Stem Cell Transplantation (HSCT) with Omidubicel Leads to Robust Recovery and Diversity of T cells" patients treated with omidubicel were found to have robust and diverse T cell constitution. In an analysis of the T-cell development of 37 patients, patients transplanted with omidubicel demonstrated higher numbers of Recent Thymic Emigrants (RTEs) in peripheral blood at one year post transplant compared to transplantation with UCB, which suggest faster thymopoiesis and provide mechanistic rational for the lower infection rates and improved outcomes in these patients. Learn more

All three posters were made available beginning Saturday, September 10, 2022, 6:15-7:45 p.m. ET, during the 2022 Cord Blood Connect Meeting.

About Omidubicel

Omidubicel is an advanced cell therapy candidate developed as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant for patients with blood cancers. Omidubicel demonstrated a statistically significant reduction in time to neutrophil engraftment in comparison to standard umbilical cord blood in an international, multi-center, randomized Phase 3 study (NCT0273029) in patients with hematologic malignancies undergoing allogeneic bone marrow transplant. The Phase 3 study also showed reduced time to platelet engraftment, reduced infections and fewer days of hospitalization. One-year post-transplant data showed sustained clinical benefits with omidubicel as demonstrated by significant reduction in infectious complications as well as reduced non-relapse mortality and no significant increase in relapse rates nor increases in graft-versus-host-disease (GvHD) rates. Omidubicel is the first stem cell transplant donor source to receive Breakthrough Therapy Designation from the FDA and has also received Orphan Drug Designation in the US and EU.

Omidubicel is an investigational stem cell therapy candidate, and its safety and efficacy have not been established by the FDA or any other health authority. For more information about omidubicel, please visit View Source

About NAM Technology

Our NAM-enabling technology is designed to enhance the number and functionality of targeted cells, enabling us to pursue a curative approach that moves beyond what is possible with existing therapies. Leveraging the unique properties of NAM (nicotinamide), we can expand and metabolically modulate multiple cell types — including stem cells and natural killer cells — with appropriate growth factors to maintain the cells’ active phenotype and enhance potency. Additionally, our NAM technology improves the metabolic fitness of cells, allowing for continued activity throughout the expansion process.

On September 12, 2022 Synthekine Inc., an engineered cytokine therapeutics company, reported that Fierce Biotech has named it as one of 2022’s Fierce 15 biotechnology companies, designating it as one of the most promising early-stage biotechnology companies in the industry (Press release, Synthekine, SEP 12, 2022, View Source [SID1234619451]).

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 are honored to be recognized as a Fierce 15 company, reflecting the potential of our distinct cytokine engineering platforms to harness the power of cytokine therapeutics," said Debanjan Ray, Chief Executive Officer of Synthekine. "I am particularly proud of the substantial progress our talented and dedicated team has made in the three years since Synthekine was founded. Looking ahead, we are eager to build upon the momentum of our maturing pipeline and continue to advance novel cytokine science for the benefit of patients with debilitating cancers and inflammatory diseases."

Synthekine recently moved STK-012, its IL-2 partial agonist, into clinical investigation and secured its first pharmaceutical partnership on its novel surrogate cytokine agonist platform. The company anticipates entering the clinic later this year with its second program, STK-009 + SYNCAR-001, to address key limitations of current CD19 CAR-T cell therapies.

The Fierce 15 celebrates the spirit of being "fierce" – championing innovation and creativity, even in the face of intense competition. This is Fierce Biotech’s 20th annual Fierce 15 selection.

An internationally recognized daily report reaching a network of over 450,000 biotech and pharma industry professionals, Fierce Biotech provides subscribers with an authoritative analysis of the day’s top stories. Every year Fierce Biotech evaluates hundreds of early-stage companies from around the world for its annual Fierce 15 list, which is based on a variety of factors such as the strength of its technology, partnerships, venture backers and a competitive market position.

On September 12, 2022 SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, reported that preclinical data supporting that tumor infiltrating lymphocytes (TILs) engineered with membrane-bound cytokines IL-2 (mbIL-2) and IL-12 (mbIL-12) may eliminate the need for the high-dose, systemic IL-2 and lymphodepleting preconditioning used with current TIL therapies (Press release, SQZ Biotech, SEP 12, 2022, View Source [SID1234619450]). SQZ TILs showed the ability to induce desirable cytokine signaling for more than 48 hours, which is comparable to the duration of exogenous IL-2 support in current TIL therapies. SQZ TILs also demonstrated improved killing of donor-matched tumor cells, upregulated markers associated with central memory T cells, and persistence in vivo. The data was presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022.

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!

"TIL therapies have shown exciting clinical results in solid tumors, but to overcome engraftment and persistence challenges they also require lymphodepletion and systemic IL-2, which are toxic to patients and prevent repeat dosing," said Jonathan Gilbert, Ph.D., Vice President of Exploratory Research at SQZ Biotechnologies. "By providing cytokine support on the surface of the cell, SQZ TILs may simultaneously eliminate the need for these toxic co-treatments and improve T cell function. Together this could potentially increase potency while also moving TILs to an outpatient procedure that allows repeat dosing and combination therapies."

The SQZ TIL platform draws from the company’s mbIL-2 and mbIL-12 constructs used in its enhanced Antigen Presenting Cell (eAPC) clinical trial. Both approaches are designed to take advantage of transient expression of membrane-bound cytokines so that potent cytokines such as IL-12 can be expressed without systemic toxicities. Additional TIL engineering with membrane-bound IL-7 (mbIL-7) and BCL-2, an anti-apoptotic factor, may further enhance the abilities of SQZ TILs to engraft without preconditioning.

Major Findings from Preclinical Research

Poster #761: Tumor Infiltrating Lymphocytes Expressing Membrane-Bound IL-2 and IL-12 Exhibit Enhanced Proliferation, Function, and Persistence Without Requiring Exogenous IL-2 Support

Cytokine Expression and Function: TILs engineered with mbIL-2 and mbIL-12 induced high levels of expression and supported >70% viability in the absence of external cytokine support for 5 days, a time greater than IL-2 is typically dosed in the clinic after TIL infusion. The membrane-bound cytokines produced an almost 4-fold expansion in vitro, which was comparable to unmodified TILs cultured in IL-2 containing media
Tumor Cell Killing: TILs from primary solid tumors engineered with mbIL-2 and mbIL-12 and subsequently cultured with donor-matched tumor cell lines showed 3.5-fold higher IFN-y release than the current clinical standard of unmodified TILs with exogenous IL-2, as well as increased tumor killing as measured by staining of apoptotic cells
Memory T Cell Reprogramming: TILs engineered to express mbIL-2 and mbIL-12 upregulated CD62L, a classical marker of central memory T cells (>80% positive, vs <20% positive for unmodified TILs at day 6). CD62L remains upregulated even after cytokine expression has diminished, suggesting a potential reprogramming of the TILs to a more memory-like state, which could positively impact T cell survival and clinical benefit
In Vivo Survival and Phenotype: mbIL-2 and mbIL-2/12 TILs adoptively transferred into a mouse model each showed more than 200% greater cell persistence in vivo as compared to unmodified TILs, and mbIL-12 drove a 3.5-fold enrichment in CD62L expression in vivo out to at least day 5 post-transfer
Promising Targets: TILs engineered with mbIL-7 and BCL2, which can support cell survival, demonstrated a strong advantage in the absence of exogenous cytokine support and could serve as potential future TIL enhancers

On September 12, 2022 Foundation Medicine, Inc., a pioneer in molecular profiling for cancer, and Relay Therapeutics (Nasdaq: RLAY), a clinical-stage precision medicine company transforming the drug discovery process by combining leading-edge computational and experimental technologies, reported a collaboration to develop FoundationOneCDx as a companion diagnostic for RLY-4008, the company’s investigational FGFR2 inhibitor (Press release, Foundation Medicine, SEP 12, 2022, View Source [SID1234619449]).

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!

RLY-4008 is a selective oral small molecule inhibitor of FGFR2, which is currently being evaluated for use in patients with FGFR2-mutated cholangiocarcinoma (CCA), or bile duct cancer, and other solid tumors. FGFR2 is one of four members of the FGFR family, a set of closely related proteins with highly similar protein sequences and properties. If the therapy and companion diagnostic are approved, FoundationOne CDx would be used to identify patients with FGFR2 fusions and select rearrangements in CCA who may be appropriate for treatment with RLY-4008.

Yesterday, at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2022 Congress, Relay presented interim clinical data for RLY-4008 from this patient population in pan-FGFR inhibitor naïve patients demonstrating an 88% overall response rate and anticipates fully enrolling this pivotal cohort in the second half of 2023.

"FGFR2-mutated cholangiocarcinoma is an aggressive condition that’s generally diagnosed in advanced stages when prognosis is poor and treatment options are limited," said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics. "We’re proud to partner with the leader in companion diagnostic approvals as we work to advance this potentially life-changing therapy and create access to it once approved."

Foundation Medicine’s portfolio of FDA-approved comprehensive genomic profiling tests offers physicians both blood- and tissue-based testing options for detecting genomic alterations that help guide personalized treatment decisions. As companion diagnostics, FoundationOne CDx and FoundationOneLiquid CDx allow oncologists to identify patients who may be appropriate for FDA-approved targeted therapies.

"Relay Therapeutics is an innovator in precision therapy development who shares our commitment to bringing more effective treatment options to patients, as expeditiously as possible," said Sanket Agrawal, Chief Biopharma Business Officer at Foundation Medicine. "We’re proud to join forces with them as they advance their novel approach to therapy development, and work to increase treatment options for patients living with cholangiocarcinoma."

The oral presentation from the ESMO (Free ESMO Whitepaper) Congress for RLY-4008 is available on the Relay Therapeutics website under Publications: View Source