On September 27, 2021 Sprint Bioscience reported that it is starting to market the DISA program to potential partners and, following a series of research advances, reveals the cancer drug program’s target protein, TREX1 (Press release, Sprint Bioscience, SEP 27, 2021, View Source [SID1234590352]). The goal of the program, currently in the preclinical phase, is to develop drugs that inhibit the protein TREX1 in order to enhance the effect of immuno-oncological therapy, radiation therapy and chemotherapy in the treatment of cancer. The company will initiate discussions with potential partners in connection with the BioEurope conference in October.

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"Inhibiting TREX1 is a unique approach with great potential to enhance the effect of several current therapies. Many modern cancer drugs depend on the immune system being able to identify the cancer cells, and with our TREX1 inhibitors, we have identified a way to stop the cancer cells’ ability to hide from the immune system. We have now reached a strong competitive position in the program’s development and look forward to discussions with potential partners."
Martin Andersson, head of research at Sprint Bioscience

Cancer cells often have elevated levels of DNA fragments that have incorrectly ended up outside the cell nucleus. Since DNA fragments that are outside the cell nucleus can activate the immune system, cancer cells depend upon these DNA fragments being rapidly removed – if they are not, the body’s immune system will attack the cancer cells.

The target protein in the Sprint Bioscience DISA project, TREX1 (three-prime repair exonuclease 1), is a protein that breaks down DNA fragments outside the cell nucleus and thus helps cancer cells escape the immune system. Scientific studies have previously shown that there is a link between elevated levels of the TREX1 protein and inferior survival for patients with certain types of cancer, including breast cancer, ovarian cancer, and pancreatic cancer.

The body’s immune response towards cancer cells can be strengthened by inhibiting TREX1, which opens up the potential to enhance the effect of other therapies such as immuno-oncology therapy, radiation therapy, and cytotoxic drug treatment. Sprint Bioscience has secured a major competitive advantage by determining the three-dimensional structure of the human TREX1 protein, not previously reported in the scientific literature. This enables the company to make full use of the power of the fragment-based technology for drug development (FBDD) that is the company’s hallmark, and at the same time further increases the opportunities to build shareholder value in this program.

"Inhibiting TREX1 is a unique approach with great potential to enhance the effect of several current therapies. Many modern cancer drugs depend on the immune system being able to identify the cancer cells, and with our TREX1 inhibitors, we have identified a way to stop the cancer cells’ ability to hide from the immune system. We have now reached a strong competitive position in the program’s development and look forward to discussions with potential partners." says Martin Andersson, Chief Scientific Officer at Sprint Bioscience.sions with potential partners." says Martin Andersson, head of research at Sprint Bioscience.

On September 27, 2021 Oblique Therapeutics reported that it has reached a key milestone in its aKRAS antibody program and achieved validation of its Abiprot platform (Press release, Oblique Therapeutics, SEP 27, 2021, https://obliquet.com/wp-content/uploads/2021/09/Oblique-Therapeutics-announces-achievement-of-key-milestone-in-its-aKRAS-mAb-program-and-Abiprot-platform-002.pdf [SID1234590351])

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Oblique Therapeutics has developed a unique, proprietary methodology Abiprot to identify epitopes on targets that have previously proven difficult to address with antibodies. Using this platform, a few epitopes were identified in KRAS, one of which encompassed the frequently mutated amino acids 12 and 13. Interestingly, this epitope is not well exposed in any of the published crystal structure of the protein. Using this epitope, Oblique Therapeutics has developed a number of potent monoclonal antibodies (mAb) that bind G13D, G12D, G12V mutant proteins selectively. Anti-G13D mAbs inhibit proliferation and cause apoptosis in a G13D mutant human colorectal cancer (CRC) cell line. Oblique is now happy to announce that it has seen good efficacy and a high degree of tumor growth inhibition of two of these aG13D mAbs in a mouse xenograft model of G13D human CRC.

This in vivo proof-of-concept is significant from two perspectives. Firstly, this validates the Abiprot platform as an important tool in identifying epitopes and generating functional antibodies against difficult targets of therapeutic interest. Secondly, this provides a high degree of confidence in progressing aG13D mAb (and mAbs against other mutants) into development for treating KRAS G13D mutant CRC and other malignancies.

Prof Owe Orwar, Founder and CEO, Oblique Therapeutics, commented, "We are truly excited by the outstanding promise we see in these results. The team led by Dr. Sreesha Srinivasa and in collaboration with Karolinska Institutet has done an exceptional job in the early phases of developing KRAS-mutant specific antibodies against three major mutations of KRAS, one of which is the driver mutation for pancreatic cancer. The in vivo proof of concept for aG13D mAb means that we will put high priority to advance this program through preclinical development aiming at clinical entry and dosing of the first patient as fast as we ever can"

About KRAS
KRAS which is mutated in approximately 20% of human cancers is the most frequently mutated oncogene. Many of the approved targeted therapies such as EGFR, HER2, RAF inhibitors do not work for KRAS mutated patients in CRC, Lung, Melanoma and other cancers. Thus, there is an urgent need to develop effective therapies for the patients harboring KRAS mutations. Mutations at residues 12 and 13 account for a vast majority of KRAS mutations. Among these, G12D, G12C, G12V and G13D are the more common amino acid substitutions. Lumakras (Amgen) has been recently approved for G12C mutated Lung cancer and another G12C inhibitor from Mirati Therapeutics is in late stages of clinical development. However, there are no drugs approved or in clinical development targeting G12D, G12V and G13D mutations.

About Abiprot
Abiprot, is a proprietary methodology to identify epitopes on protein targets that have previously proven difficult to address with antibodies. Abiprot can identify high-affinity antibody binding sites in a given protein with single amino acid resolution while the protein resides in its native environment. It is based on using a tailored molecular reporter system and proteomics. The platform yields detailed sequence and structure information for epitope identification and development. Oblique Therapeutics is applying this technology for discovery of a new generation of selective antibody therapeutics targeting cancer and pain

On September 27, 2021 Omega Therapeutics, Inc. (Nasdaq: OMGA) ("Omega"), a development-stage biotechnology company pioneering the first systematic approach to use mRNA therapeutics as programmable epigenetic medicines by leveraging its OMEGA Epigenomic Programing platform, reported that Mahesh Karande, President and Chief Executive Officer, will participate in a fireside chat at the Chardan Virtual 5th Annual Genetic Medicines Conference on Monday, October 4, 2021 at 8:30 a.m. ET (Press release, Omega Therapeutics, SEP 27, 2021, View Source [SID1234590345]).

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A live webcast of the fireside chat will be available on the Investors & Media section of the Company’s website at www.omegatherapeutics.com. An archived replay of the fireside chat will be available on the same website for approximately 90 days.

On September 27, 2021 JW Therapeutics (HKEx: 2126), an innovative biotechnology company focused on developing, manufacturing and commercializing cell immunotherapy products, reported that it has received the Investigational New Drug (IND) clearance from the National Medical Products Administration (NMPA) of China for a clinical trial of BCMA-targeted Chimeric Antigen Receptor (CAR) T cell JWCAR129 in treating relapsed or refractory multiple myeloma (R/R MM) (Press release, JW Therapeutics, SEP 27, 2021, View Source [SID1234590344]).

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Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells. Although treatment may result in remission, unfortunately, patients will most likely relapse. While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections. Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options available. As a result, there is a significant unmet need for patients with R/R MM.

References:

American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: View Source Accessed November 2020.
Abdi J, Chen G, Chang H, et al. Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms. Oncotarget. 2013;4:2186–2207.
American Cancer Society. Multiple myeloma: early detection, diagnosis and staging. Available at: View Source Accessed November 2020.
Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012;26:149-57.

On September 27, 2021 the Barbara Ann Karmanos Cancer Institute reported that it will celebrate its 27th annual Partners Event highlighting the importance of cancer research (Press release, Karmanos Cancer Institute, SEP 27, 2021, View Source [SID1234590340]).

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The night will feature an electric live performance from Collision Six, powerful presentations and an incredible auction with all proceeds benefiting Karmanos Cancer Institute.

Partners Night will feature an electric live performance from Collision Six, powerful presentations and an incredible auction with all proceeds benefiting Karmanos Cancer Institute.
Partners Night will feature an electric live performance from Collision Six, powerful presentations and an incredible auction with all proceeds benefiting Karmanos Cancer Institute.
Partners Night 2021 is virtual and is free for everyone.

To register, donate and participate go to Partners21.givesmart.com.

Partners 2021
All funds raised through sponsorships, donations and the auction will support the work of a multidisciplinary team of applied, clinical and basic scientists who are focused on addressing racial healthcare disparities associated with lung cancer and response to treatment with immunotherapy. This comprehensive initiative will assess how immunotherapy differentially affects African American and white lung cancer patients and the extent to which there are differential biological, psychological and social drivers by race of treatment response. This research has the potential to identify race-specific factors that could be used to drive treatment decision-making and clinical follow-up.

Since the Partners Committee began, Partners Events have raised more than $17 million to support Karmanos’ world-renowned scientists in conducting ground-breaking research, which helps lead to new and advanced treatment options and supportive post-treatment care for cancer survivors.

Event Details
Thursday, September 30, 2021, 6 – 8:30 p.m.
6 – 6:30 p.m. live performance by Collision Six
6:30 – 7:30 p.m. presentations
7:30 p.m. auction
Closing performance by Collision Six following the auction

Auction items are now live! To view, register and start bidding, go to www.karmanos.org/partners.

Please email [email protected] with any questions.

How Partners Started
Karmanos Cancer Institute long-time supporters Anna and Harry Korman had the vision to begin Partners in memory of their late daughter Suzanne who died of cancer at the age of 36. The Kormans established the committee as a way to engage young people in raising money for cancer research, knowing that research would lead to advancements in treatment options and early detection methods.

The Kormans’ daughter and son-in-law Eunice and Milton Ring and other family members continue the Kormans’ legacy along with the Partners Committee. The Partners are united in the fight against cancer and are dedicated to solely raising funds for research at Karmanos Cancer Institute, a subsidiary of McLaren Health Care, through the annual signature fundraiser known as The Partners Event.