nectin-4 x TOP1

INDIANAPOLIS, Oct. 4, 2023 /PRNewswire/ -- Loxo@Lilly, the oncology unit of Eli Lilly and Company (NYSE: LLY), today announced that preclinical data for agents targeting KRAS G12D, multiple oncogenic KRAS mutations and Nectin-4, will be presented at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, taking place October 11-15, 2023, in Boston. These programs are among the next slate of new oncology agents planned to enter clinical trials for Loxo@Lilly in 2024. The poster presentations will include preclinical characterization data for a highly potent inhibitor of KRAS G12D that is selective against wild-type KRAS, a highly potent and isoform-selective pan-KRAS inhibitor with activity against a broad spectrum of the most common activating KRAS mutations and high selectivity over wild-type HRAS and NRAS, and a fully human monoclonal anti-Nectin-4 antibody conjugated to a topoisomerase I (TOPO 1) inhibitor. "This marks the first preclinical data for three of the new molecules planned to enter clinical trials next year in areas of cancer biology with continued need for new and better treatment options," said Jacob Van Naarden, president, Loxo@Lilly. "These new programs represent years of focused work to create differentiated molecules against exacting target product profiles. We look forward to moving these programs into the clinic over the next year." Details on poster presentations are below: Presentation Title: Preclinical characterization of LY3962673, an orally bioavailable, highly potent, and selective KRAS G12D inhibitor Abstract Number: B115 Presentation Date & Time: Friday October 13, 12:30pm – 4:00pm ET Session: Poster Session B Presenter: Chandrasekar Iyer Presentation Title: Preclinical characterization of orally bioavailable, highly potent pan-KRAS inhibitors with selectivity over HRAS and NRAS Abstract Number: B116 Presentation Date & Time: Friday October 13, 12:30pm – 4:00pm ET Session: Poster Session B Presenter: Lourdes Prieto Vallejo Presentation Title: Preclinical characterization of ETx-22, a next-generation antibody drug conjugate (ADC) targeting Nectin-4 Abstract Number: B128 Presentation Date & Time: Friday October 13, 12:30pm – 4:00pm ET Session: Poster Session B Presenter: Joanna Fares About Lilly Lilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer's disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news or follow us on Facebook, Instagram, Twitter and LinkedIn. P-LLY Lilly Forward-Looking Statement This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Lilly's oncology pipeline, including therapies under development, and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there can be no guarantee that studies will be initiated or completed as planned, that future study results will be consistent with the results to date, or that any of these therapies will receive initial regulatory approvals or approvals for additional indications, as applicable, or be commercially successful. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. © Lilly USA, LLC 2023. ALL RIGHTS RESERVED. SOURCE Eli Lilly and Company

AU ZH, Switzerland, April 14, 2023 (GLOBE NEWSWIRE) -- Araris Biotech AG, a company pioneering a proprietary antibody-drug conjugate (ADC)-linker technology, today announced the company will deliver two poster presentations at this year’s American Association for Cancer Research (AACR) 2023 Annual Meeting, being held April 14-19, 2023 at the Orange County Convention Center in Orlando, Florida. The presentations will highlight late-breaking preclinical data on anti-Nectin-4 and anti-HER2 ADCs generated using the company’s proprietary linker technology. Both ADCs demonstrated improved anti-tumor activity compared to respective FDA approved ADCs in head-to-head in-vivo studies. "The preclinical data highlighted in these two presentations demonstrate that we can develop stable and highly efficacious ADCs with a low drug-load that have an excellent exposure, which we believe may enable us to address key dose-limiting toxicities,” said Philipp Spycher, Ph.D., co-founder and chief executive officer of Araris Biotech AG. “Our ADCs have the potential to address challenges seen amongst other currently approved ADC therapies, such as limited efficacy and tolerability, in addition to being able to display favorable biophysical properties. We are looking forward to studying our linker technology further and continuing to advance our Nectin-4 program.” The poster presentation titled “Novel peptide linker-based Nectin-4 targeting ADC shows improved tolerability with long-lasting anti-tumor efficacy at low doses” will be presented on April 18, 2023 from 9:00 a.m. to 12:30 p.m. ET. The poster will be presented by Isabella Attinger-Toller, Ph.D. co-founder and chief technology officer at poster board number 12, abstract number LB219. Poster presentation highlights: Generated an anti-Nectin-4 ADC based on enfortumab as the targeting antibody with monomethyl auristatin E (MMAE) as the payload using Araris’ peptide linker and site-specific enzymatic conjugation approach Resulting ADC had a drug-to-antibody-ratio (DAR) of 2. By comparison, the approved enfortumab-vedotin (EV) used a higher payload amount, with a DAR of 4. Araris’ ADC demonstrated potent cell cytotoxicity similar to EV, despite using lower drug load, as well as excellent stability in mouse and human sera exemplified by the absence of payload deconjugation or linker cleavage. EV showed significant payload deconjugation Using a breast cancer model, Araris’ ADC demonstrated a complete tumor regression lasting for more than 100 days. EV administered at the same payload dose showed only a short and transient (20 day) tumor regression with no animal reaching a complete response. Despite higher in vivo exposure and extremely efficient anti-tumor response at low payload doses, there was no increased toxicity from the Araris ADC. Overall tolerability improved compared to EV The poster presentation titled “Inducing significant and efficient tumor growth inhibition vs. trastuzumab deruxtecan with low drug-load Topoisomerase 1 inhibitor ADC using novel peptide linkers for payload conjugation” will be presented on April 18, 2023 from 9:00 a.m. to 12:30 p.m. ET. The poster will be presented by Philipp Spycher, Ph.D. co-founder and chief executive officer at poster board number 14, abstract number LB221. Poster presentation highlights: Generated an anti-HER2 ADC based on trastuzumab as the targeting antibody with Topoisomerase 1 (Topo1) inhibitor as payload, using Araris’ peptide linker and site-specific enzymatic conjugation approach Resulting ADC had a drug-to-antibody-ratio (DAR) of 2. By comparison, the approved Trastuzumab deruxtecan used a higher payload amount, with a DAR of 8. Araris’ ADC demonstrated potent cell cytotoxicity despite using lower drug load, as well as a pharmacokinetic-pro to the naked antibody. Trastuzumab deruxtecan showed faster clearance. Using a colon cancer model, the Araris ADC demonstrated superior anti-tumor activity compared to Trastuzumab deruxtecan, injected at the same payload doses. Araris’ ADC resulted in complete tumor regression lasting the entirety of the study (80 days) and was well tolerated. About Araris Biotech AG Araris Biotech AG is pioneering the development of its novel antibody-drug conjugate (ADC)-linker technology to enable efficient and precise production of ADCs. Its linker platform enables the attachment of any drug payload to ‘off the shelf’ antibodies, without the need for prior antibody engineering. The resulting ADCs have shown very high activity at low doses and an improved therapeutic index compared to FDA-approved ADCs. Araris is a spin-off company from the Paul Scherrer Institute (PSI) and ETH Zurich. For more information, please visit or follow Araris on Twitter and LinkedIn. Corporate Contact: Philipp Spycher, Ph.D. Chief Executive Officer info@ararisbiotech.com Media Contact: Veronica Eames LifeSci Communications, LLC veames@lifescicomms.com 646-970-4682

Two late-breaking abstracts will be presentedAU ZH, Switzerland, April 14, 2023 (GLOBE NEWSWIRE) -- Araris Biotech AG, a company pioneering a proprietary antibody-drug conjugate (ADC)-linker technology, today announced the company will deliver two poster presentations at this year’s American Association for Cancer Research (AACR) 2023 Annual Meeting, being held April 14-19, 2023 at the Orange County Convention Center in Orlando, Florida. The presentations will highlight late-breaking preclinical data on anti-Nectin-4 and anti-HER2 ADCs generated using the company’s proprietary linker technology. Both ADCs demonstrated improved anti-tumor activity compared to respective FDA approved ADCs in head-to-head in-vivo studies. "The preclinical data highlighted in these two presentations demonstrate that we can develop stable and highly efficacious ADCs with a low drug-load that have an excellent exposure, which we believe may enable us to address key dose-limiting toxicities,” said Philipp Spycher, Ph.D., co-founder and chief executive officer of Araris Biotech AG. “Our ADCs have the potential to address challenges seen amongst other currently approved ADC therapies, such as limited efficacy and tolerability, in addition to being able to display favorable biophysical properties. We are looking forward to studying our linker technology further and continuing to advance our Nectin-4 program.” The poster presentation titled “Novel peptide linker-based Nectin-4 targeting ADC shows improved tolerability with long-lasting anti-tumor efficacy at low doses” will be presented on April 18, 2023 from 9:00 a.m. to 12:30 p.m. ET. The poster will be presented by Isabella Attinger-Toller, Ph.D. co-founder and chief technology officer at poster board number 12, abstract number LB219. Poster presentation highlights: Generated an anti-Nectin-4 ADC based on enfortumab as the targeting antibody with monomethyl auristatin E (MMAE) as the payload using Araris’ peptide linker and site-specific enzymatic conjugation approachResulting ADC had a drug-to-antibody-ratio (DAR) of 2. By comparison, the approved enfortumab-vedotin (EV) used a higher payload amount, with a DAR of 4.Araris’ ADC demonstrated potent cell cytotoxicity similar to EV, despite using lower drug load, as well as excellent stability in mouse and human sera exemplified by the absence of payload deconjugation or linker cleavage. EV showed significant payload deconjugationUsing a breast cancer model, Araris’ ADC demonstrated a complete tumor regression lasting for more than 100 days. EV administered at the same payload dose showed only a short and transient (20 day) tumor regression with no animal reaching a complete response.Despite higher in vivo exposure and extremely efficient anti-tumor response at low payload doses, there was no increased toxicity from the Araris ADC. Overall tolerability improved compared to EV The poster presentation titled “Inducing significant and efficient tumor growth inhibition vs. trastuzumab deruxtecan with low drug-load Topoisomerase 1 inhibitor ADC using novel peptide linkers for payload conjugation” will be presented on April 18, 2023 from 9:00 a.m. to 12:30 p.m. ET. The poster will be presented by Philipp Spycher, Ph.D. co-founder and chief executive officer at poster board number 14, abstract number LB221. Poster presentation highlights: Generated an anti-HER2 ADC based on trastuzumab as the targeting antibody with Topoisomerase 1 (Topo1) inhibitor as payload, using Araris’ peptide linker and site-specific enzymatic conjugation approachResulting ADC had a drug-to-antibody-ratio (DAR) of 2. By comparison, the approved Trastuzumab deruxtecan used a higher payload amount, with a DAR of 8.Araris’ ADC demonstrated potent cell cytotoxicity despite using lower drug load, as well as a pharmacokinetic-profile similar to the naked antibody. Trastuzumab deruxtecan showed faster clearance.Using a colon cancer model, the Araris ADC demonstrated superior anti-tumor activity compared to Trastuzumab deruxtecan, injected at the same payload doses. Araris’ ADC resulted in complete tumor regression lasting the entirety of the study (80 days) and was well tolerated. About Araris Biotech AG Araris Biotech AG is pioneering the development of its novel antibody-drug conjugate (ADC)-linker technology to enable efficient and precise production of ADCs. Its linker platform enables the attachment of any drug payload to ‘off the shelf’ antibodies, without the need for prior antibody engineering. The resulting ADCs have shown very high activity at low doses and an improved therapeutic index compared to FDA-approved ADCs. Araris is a spin-off company from the Paul Scherrer Institute (PSI) and ETH Zurich. For more information, please visit www.ararisbiotech.com or follow Araris on Twitter and LinkedIn. Corporate Contact:Philipp Spycher, Ph.D.Chief Executive Officerinfo@ararisbiotech.comwww.ararisbiotech.com Media Contact:Veronica EamesLifeSci Communications, LLC veames@lifescicomms.com646-970-4682