This phase Ib/II trial evaluates the safety and effect of the Nous-209 vaccine in Lynch syndrome patients. Lynch syndrome is an inherited disorder in which affected individuals have a higher-than-normal chance of developing colorectal cancer and certain other types of cancer, often before the age of 50. In Lynch syndrome, errors in the genetic information inside cells are not properly corrected. When that happens, the cells produce new proteins called neoantigens. Neoantigens are recognized by the body's immune system as foreign, and the body tries to get rid of them. Nous-209 is a vaccine made with man-made copies of some of those neoantigens. This trial aims to see whether the Nous-209 vaccine is safe to give to patients with Lynch syndrome, whether people are able to take the Nous-209 vaccine without becoming too uncomfortable, and how the immune system of patients with Lynch syndrome respond to the Nous-209 vaccine. This trial may help researchers determine whether receiving Nous-209 have an effect on the development of polyps or tumors in the colon.

Start Date10 Nov 2022

Sponsor / Collaborator

National Cancer Institute

NCT04041310 / RecruitingPhase 1/2

A Phase I/II, Multicenter, Open-Label Study of Nous-209 Genetic Vaccine for the Treatment of Microsatellite Unstable Solid Tumors

Ref: Protocol v9.0, dated 7Nov2023. NOUS-209-01 is a multicenter, open-label, multiple cohorts, clinical study, designed to evaluate safety, tolerability, and immunogenicity, and to detect any preliminary evidence of anti-tumor activity of Nous-209 genetic polyvalent vaccine plus pembrolizumab combination therapy in adult subjects with unresectable or metastatic deficient mismatch repair (dMMR) or MSI-H CRC, gastric, or gastro-esophageal junction (G-E junction) tumors. Nous-209 is based on a heterologous prime/boost regimen composed of the Great Ape Adenovirus GAd20-209-FSP used for priming and Modified Vaccinia virus Ankara MVA-209-FSP used for boosting. The Phase I portion of the study is a first-in-human (FIH) clinical study with a primary objective to elucidate the safety and tolerability of Nous-209 in addition to establishing the recommended Phase 2 dose (RP2D), whereas the Phase II was introduced to assess efficacy as the primary objective.

Start Date21 Oct 2019

Sponsor / Collaborator

Nouscom AGStartup

[+1]

100 Clinical Results associated with MVA-209-FSP

100 Translational Medicine associated with MVA-209-FSP

100 Patents (Medical) associated with MVA-209-FSP

Literatures (Medical) associated with MVA-209-FSP

15 Sep 2020·Cancer researchQ1 · MEDICINE

A Genetic Vaccine Encoding Shared Cancer Neoantigens to Treat Tumors with Microsatellite Instability

Q1 · MEDICINE

Article

Author: Merone, Rossella ; Mori, Federica ; Troise, Fulvia ; Langone, Francesca ; van der Bruggen, Pierre ; Yadav, Mahesh ; Vanhaver, Cristophe ; Tucci, Fabio Giovanni ; De Lucia, Maria ; Vitale, Rosa ; Folgori, Antonella ; Colloca, Stefano ; D'Alise, Anna Morena ; Ruzza, Valentino ; Leuzzi, Adriano ; Catanese, Maria Teresa ; Nicosia, Alfredo ; Lahm, Armin ; Garzia, Irene ; Di Matteo, Elena ; Bignone, Veronica ; Gordon-Alonso, Monica ; Abbate, Adele ; Diodoro, Maria Grazia ; Soprana, Elisa ; Scarselli, Elisa ; Siccardi, Antonio ; Cotugno, Gabriella ; Fichera, Imma ; Panigada, Maddalena ; Leoni, Guido

Abstract:

Tumors with microsatellite instability (MSI) are caused by a defective DNA mismatch repair system that leads to the accumulation of mutations within microsatellite regions. Indels in microsatellites of coding genes can result in the synthesis of frameshift peptides (FSP). FSPs are tumor-specific neoantigens shared across patients with MSI. In this study, we developed a neoantigen-based vaccine for the treatment of MSI tumors. Genetic sequences from 320 MSI tumor biopsies and matched healthy tissues in The Cancer Genome Atlas database were analyzed to select shared FSPs. Two hundred nine FSPs were selected and cloned into nonhuman Great Ape Adenoviral and Modified Vaccinia Ankara vectors to generate a viral-vectored vaccine, referred to as Nous-209. Sequencing tumor biopsies of 20 independent patients with MSI colorectal cancer revealed that a median number of 31 FSPs out of the 209 encoded by the vaccine was detected both in DNA and mRNA extracted from each tumor biopsy. A relevant number of peptides encoded by the vaccine were predicted to bind patient HLA haplotypes. Vaccine immunogenicity was demonstrated in mice with potent and broad induction of FSP-specific CD8 and CD4 T-cell responses. Moreover, a vaccine-encoded FSP was processed in vitro by human antigen-presenting cells and was subsequently able to activate human CD8 T cells. Nous-209 is an “off-the-shelf” cancer vaccine encoding many neoantigens shared across sporadic and hereditary MSI tumors. These results indicate that Nous-209 can induce the optimal breadth of immune responses that might achieve clinical benefit to treat and prevent MSI tumors.

Significance::

These findings demonstrate the feasibility of an “off-the-shelf” vaccine for treatment and prevention of tumors harboring frameshift mutations and neoantigenic peptides as a result of microsatellite instability.

News (Medical) associated with MVA-209-FSP

14 May 2024

·www.biospace.com

Nouscom Appoints Leading Cancer Drug Development Expert, Neil Gallagher, MD, PhD, as Independent Advisor to its Board and Chair of its R&D Committee

Dr. Gallagher, current President of R&D at Syndax Pharmaceuticals and former Chief Medical Officer and Head of Development at AbbVie, brings significant experience of end-to-end development that has resulted in the approval of multiple innovative medicines BASEL, Switzerland – 14th May 2024 - Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized viral vector-based cancer vaccines targeting neoantigens, announces today that Neil Gallagher, MD, PhD, has been appointed as an Independent Advisor to Nouscom’s Board of Directors and will also Chair the Company’s R&D Committee. Dr. Gallagher’s leadership will be essential in guiding Nouscom’s clinical development strategy and activities as it advances its wholly owned clinical pipeline through multiple clinical proof of concept readouts. Dr. Gallagher has over 20 years of experience within large, global pharmaceutical R&D organizations and emerging biopharmaceutical companies. Throughout his career, he has led end-to-end drug development programs that have resulted in the approval of multiple innovative medicines, ranging from small molecules to biologics across several therapeutic areas, including oncology and immunology. Since April 2023, he has served as President of R&D at Syndax Pharmaceuticals, a clinical-stage oncology company developing targeted first-in-class cancer therapies. Prior to this, he led multiple development programs through approval globally and oversaw asset strategy and portfolio management across several therapeutic areas as Chief Medical Officer and Head of Development at AbbVie. Other roles include Head of Global Oncology Development at AbbVie, Head of Development for Oncology and Inflammation at Amgen, and Global Program Head at Novartis Oncology. He has also held clinical development roles at AstraZeneca and Astex Therapeutics. Before entering the industry, Dr. Gallagher received his medical degree from Trinity College, Dublin, and completed his Fellowship in Gynaecological Oncology at the Institute for Cancer Studies, University of Birmingham, UK. Dr. Marina Udier, Chief Executive Officer of Nouscom, commented, “We are thrilled to welcome Neil as Independent Advisor to our Board and Chair of our R&D Committee. His extensive experience and leadership in clinical drug development and registration will provide invaluable insights that will allow us to further accelerate progress across our clinical portfolio of neoantigen-based cancer vaccines, including an ongoing randomized Phase 2 trial of NOUS-209 in MSI colorectal cancer.” Dr. Goran Ando, Independent Chair of Nouscom’s Board, said, “Together with the experience of our existing Board Members, I look forward to Neil’s contributions as Nouscom reports multiple clinical trial readouts and navigates the next exciting steps in its growth.” Dr. Neil Gallagher added, “I am truly excited to be working with Nouscom’s Board and management and look forward to sharing my knowledge and expertise to guide and support the development of its clinical pipeline. Nouscom’s dedication to generating safe, innovative, and potent next-generation cancer immunotherapies that selectively eliminate tumor cells and pre-cancerous lesions could be potentially life-changing for patients and I look forward to helping the Company achieve this.” Ends About Nouscom Nouscom is a clinical-stage immuno-oncology company developing next-generation, off-the-shelf and personalized cancer immunotherapies. Nouscom’s proprietary viral vector platform has the capacity to encode for large payloads of neoantigens or other immunomodulators and clinically demonstrated to safely and potently harness the power of the immune system. Nouscom is currently advancing the clinical development of its wholly owned programs: NOUS-209, an off-the-shelf cancer immunotherapy for the treatment of MSI solid tumors in combination with pembrolizumab in randomized Phase 2 trials. NOUS-209, an off-the-shelf monotherapy in Lynch Syndrome carriers with the potential to ‘intercept cancer’ before it occurs. A Phase 1b is being conducted under a clinical trial collaboration and supply agreement signed in 2022 with the National Cancer Institute (NCI). NOUS-PEV, a personalized cancer immunotherapy, is expected to enter randomized Phase 2 trials in indications with high unmet medical need in 2024. Nouscom has also exclusively out-licensed VAC-85135, an off-the-shelf immunotherapy developed under a multi-project agreement, which is currently under evaluation in a Phase 1 trial for the treatment of Myeloproliferative Neoplasms sponsored by Janssen Research & Development and Bristol Myers Squibb. For more information on Nouscom, please visit the company’s website at or follow us on LinkedIn. Contacts Nouscom Rick Davis, COO E : info@nouscom.com T : +41 61 201 1835 MEDiSTRAVA Sylvie Berrebi, Mark Swallow E : nouscom@medistrava.com T : +44 (0)203 928 6900

Phase 1VaccinePhase 2ImmunotherapyExecutive Change

21 Mar 2024

·www.biospace.com

Angelini Ventures invests into extended €75.8 million ($82 million) Series C financing round for Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized cancer vaccines

Angelini Ventures joins syndicate of top-tier international healthcare investors in Nouscom’s Series C financing round Financing will enable Nouscom to continue advancing the clinical development of its portfolio of neoantigen cancer vaccines to key clinical proof-of-concept endpoints Participation in this financing marks Angelini Ventures’ fourth life sciences investment in 2024 and its 15th since launching its €300 million BioTech and Digital Health fund in 2022 Rome, Italy, 21 March 2024 – Angelini Ventures, the corporate venture firm of Angelini Industries focused on investing in companies developing innovative solutions and ideas in BioTech and Digital Health, is pleased to announce its participation in an extension of the Series C financing round for Nouscom, a clinical stage immuno-oncology company based in Basel, Switzerland. Angelini Ventures’ investment of €7 million brings the total raised by Nouscom, in its oversubscribed Series C round – first announced in November 2023 – to €75.8 million (approx. $82 million). Angelini Ventures joins a syndicate of top-tier international healthcare investors through its participation in Nouscom’s financing, including new investors: Andera Partners, Bpifrance (through its InnoBio 2 fund), M Ventures, Revelation Partners, Indaco Venture Partners, Panakès Partners, XGen Ventures; existing investors: 5AM Ventures, EQT Life Sciences, Versant Ventures; and other undisclosed investors. The total proceeds of the Series C financing will enable Nouscom to continue advancing and expanding its wholly owned clinical pipeline to achieve multiple clinical value catalysts including: Readout from its ongoing randomized Phase 2 clinical trial for NOUS-209, an off-the-shelf cancer vaccine for the treatment of Mismatch Repair/Microsatellite Instable (dMMR/MSI) Metastatic Colorectal Cancer (mCRC) Phase 1b study completion and progression of NOUS-209 monotherapy in Lynch Syndrome (LS) carriers investigating the potential to intercept, prevent or delay cancer in high-risk individuals Phase 1b study completion for NOUS-PEV, a personalized cancer immunotherapy, in combination with a checkpoint inhibitor in patients with advanced melanoma and entry into randomized Phase 2 trials in indications with high unmet medical needs. Paolo Di Giorgio, Chief Executive Officer at Angelini Ventures, said: “In less than two years since launching our healthcare focused venture strategy, we have executed 15 global investments spanning biotechnology to digital health. Our aim is to promote innovation by investing in a portfolio of high-quality companies in Europe and North America that are transforming healthcare to improve patient outcomes. Our investment in Nouscom is a great example of the type of company we are interested in. We have been highly impressed with Nouscom’s team, best-in-class technology and advancing clinical pipeline, which is expected to deliver multiple catalysts in the coming years and, if positive, exciting new immunotherapy options for cancer patients.” Dr. Marina Udier, Chief Executive Officer at Nouscom, commented: “We are delighted to have extended our successful Series C financing round and excited to have Angelini Ventures on board. Their support strengthens our commitment to innovation and accelerates our journey towards delivering next-generation treatments for cancer patients.” Sergio Marullo di Condojanni, Chief Executive Officer of Angelini Industries, added: “As shareholders of Angelini Ventures, we look at opportunities that can be interesting not only in terms of return on investment but also to support ideas and new projects able to design high-impact solutions. This kind of investment fully responds to our long-term vision which is to take care of patients, communities, and nations, aiming to transform the future of the global health system.” *** Notes to Editors About Angelini Ventures Angelini Ventures, the venture capital arm of Angelini Industries, is an early-stage investment firm focused on accelerating disruptive innovations and trends in BioTech and Digital Health. The firm will invest €300 million across a global portfolio led by investment professionals and advisors in Europe, North America, and Asia. Angelini Ventures has deep domain expertise and leverages a global team, advisors, and strategic partners to help entrepreneurs scale their businesses into transformative category-leading companies. To date, Angelini Ventures has invested €80 million into 15 companies (five of which were created with Angelini Lumira Biosciences Fund) covering a range of therapeutic areas and modalities, including Cour Pharmaceuticals, Noctrix Health, Avation Medical, Pretzel Therapeutics, Cadence Neuroscience and Freya Biosciences. About Angelini Industries Angelini Industries is a multinational industrial group founded in Ancona in 1919 by Francesco Angelini. Today, Angelini Industries represents a solid and diversified industrial reality that employs approximately 5,800 employees and operates in 21 countries around the world with revenues of over 2 billion euros, generated in the health, industrial technology and consumer goods sectors. A targeted investment strategy for growth, constant commitment to research and development, deep knowledge of markets and business sectors, make Angelini Industries one of the Italian companies of excellence in the sectors in which it operates. About Nouscom Nouscom is a clinical-stage immuno-oncology company developing next-generation, off-the-shelf and personalized cancer immunotherapies. Nouscom’s proprietary viral vector platform has the capacity to encode for large payloads of neoantigens or other immunomodulators and clinically demonstrated to safely and potently harness the power of the immune system. Nouscom is currently advancing the clinical development of its wholly owned programs: NOUS-209, an off-the-shelf cancer immunotherapy for the treatment of MSI solid tumors in combination with pembrolizumab in randomized Phase 2 trials. In January 2023, Nouscom announced a clinical trial collaboration and pembrolizumab supply agreement with MSD (Merck & Co., Inc., Rahway, NJ, USA). NOUS-209, an off-the-shelf monotherapy in Lynch Syndrome carriers with the potential to ‘intercept cancer’ before it occurs. A Phase 1b is being conducted under a clinical trial collaboration and supply agreement signed in 2022 with the National Cancer Institute (NCI) and a randomized Phase 2 trial is expected to be initiated in 2024. NOUS-PEV, a personalized cancer immunotherapy, is expected to enter randomized Phase 2 trials in indications with high unmet medical need in 2024. Nouscom has also exclusively out-licensed VAC-85135, an off-the-shelf immunotherapy developed under a multi-project agreement, which is currently under evaluation in a Phase 1 trial for the treatment of Myeloproliferative Neoplasms sponsored by Janssen Research & Development and Bristol Myers Squibb. For more information on Nouscom, please visit the company’s website at or follow us on LinkedIn. Contacts Angelini Ventures Paolo Di Giorgio, CEO Martina Palmese, Communications Coordinator martina.palmese@angeliniventures.com SEC Newgate Italia Daniele Pinosa daniele.pinosa@secnewgate.it Tel. +39 3357233872 Fausta Tagliarini fausta.tagliarini@secnewgate.it Tel. +39 3476474513 Daniele Murgia daniele.murgia@secnewgate.it Tel. +39 3384330031 MEDiSTRAVA (for press outside Italy) Sylvie Berrebi, Sandi Greenwood, Mark Swallow Sylvie.berrebi@medistrava.com Nouscom Rick Davis, COO info@nouscom.com

Phase 2ImmunotherapyPhase 1Vaccine

19 Apr 2023

·www.biospace.com

Nouscom Presents New Positive Translational Phase 1b Data of NOUS-PEV, a Personalized Neoantigen Cancer Immunotherapy, in a Late-Breaking Abstract at AACR 2023

NOUS-PEV demonstrated good safety and immunogenicity, and induced durable neoantigen-specific T cell responses that were detected for over 6 months and increased T cell infiltration in tumors demonstratingpositive anti-tumor activity in solid tumors BASEL, Switzerland – 18thApril2023 - Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized viral vector immunotherapies, today announced new translational and biomarker data obtained from the ongoing Phase 1b trial evaluating NOUS-PEV in patients with metastatic melanoma. The data will be presented today in a Late-Breaking session at the 2023 American Association for Cancer Research (AACR) Annual Meeting. Dr. Elisa Scarselli, Chief Scientific Officer and Co-Founder of Nouscom, said: “These translational data presented at AACR demonstrate NOUS-PEV, in combination withpembrolizumab,induces long-lasting, tumor-infiltrating memory T cells and anti-tumor activityin metastatic melanoma patients, further supportingthe mechanism of actions driving clinical efficacy.Ourresults further validate the immunogenic potency of our viral vector platform targeting shared and personalized neoantigens. We look forward to advancing the clinical development of NOUS-PEV and reporting complete Phase 1 results later this year.” The abstract reports a greater than 90% success in manufacturing feasibility with a median vaccine release of 8 weeks from biopsy. NOUS-PEV was demonstrated to be safe, well tolerated and highly immunogenic, inducing potent neoantigen-specific CD4 and CD8 T cell responses that were detected for greater than six months in all evaluable patients. Biomarker analysis demonstrated neoantigen-specific increased T cell migration and infiltration in tumors in patients with durable clinical responses. Current clinical efficacy data from six melanoma patients with 11 months median follow up demonstrated 4 partial responses, 1 durable stable disease and 1 progressive disease. PosterPresentation Details: Title: NOUS-PEV, a Personalized Cancer Immunotherapy targeting neoantigens, induces long lasting, tumor infiltrating memory T cells The abstract is available here. Ends About NOUS-PEV NOUS-PEV is a personalized cancer immunotherapy designed for each patient based on selection and prioritization of mutations unique to that patient’s tumor. The strategy is based on Nouscom’s heterologous prime boost platform clinically validated by its lead off-the-shelf clinical development program NOUS-209. The platform is composed of a proprietary non-human adenoviral vector (GAd) and Modified Vaccinia Ankara viral vector (MVA). Each of the two viral vectors have the capacity to encode up to 60 personalized neoantigens selected and prioritized using the VENUS (Vaccine-Encoded Neontigens Unrestricted Selection) 1 proprietary algorithm. NOUS-PEV is being evaluated in a Phase 1b (NCT04990479) clinical trial assessing the safety, feasibility and efficacy as per RECIST 1.1 criteria in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab, in patients with either locally advanced 1L melanoma or 1L non-small cell lung cancer (NSCLC) expressing more than 50% PD-L1. 1. Leoni et al. VENUS, a Novel Selection Approach to Improve the Accuracy of Neoantigens’ Prediction. Vaccines 9, 2021 About Nouscom Nouscom is a clinical stage immuno-oncology company developing next-generation, off-the-shelf and personalized cancer immunotherapies. Nouscom’s proprietary viral vector platform has the capacity to encode for large payloads of neoantigens or other immunomodulators and to safely and potently harness the power of the immune system. Nouscom is currently advancing the clinical development of its wholly owned programs: NOUS-209, an off-the-shelf cancer immunotherapy for the treatment of MSI-H solid tumors in combination with pembrolizumab NOUS-209, an off-the-shelf monotherapy in Lynch Syndrome Carriers with potential to ‘intercept cancer’ before it occurs NOUS-PEV, a personalized cancer immunotherapy for the treatment of advanced melanoma or lung cancer Nouscom has also exclusively out-licensed VAC-85135, an off-the-shelf immunotherapy developed under a multi-project agreement, which is currently under evaluation in a Phase 1 trial for the treatment of Myeloproliferative Neoplasms sponsored by Janssen Research & Development and Bristol-Myers Squibb. For more information on Nouscom, please visit the company’s website at or follow us on LinkedIn. Contacts Nouscom Rick Davis, COO E : info@nouscom.com T : +41 61 201 1835 MEDiSTRAVA Consulting Sylvie Berrebi, Eleanor Perkin E : nouscom@medistrava.com T : +44 (0)203 928 6900

ImmunotherapyPhase 1AACRVaccine

100 Deals associated with MVA-209-FSP

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Hereditary Nonpolyposis Colorectal Cancer	Phase 2	US	National Cancer Institute	10 Nov 2022
Hereditary Nonpolyposis Colorectal Cancer	Phase 2	PR	National Cancer Institute	10 Nov 2022
Microsatellite Instability cancer	Phase 1	US	Nouscom AGStartup	21 Oct 2019
Metastatic Colorectal Carcinoma	Phase 1	-	Nouscom AGStartup	-

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04041310 (NOUS-209-01, ASCO2023) Manual	Phase 1/2	Microsatellite instability-high colorectal cancer First line Deficient DNA Mismatch Repair (dMMR) \| MSI-High	7	Pembrolizumab+NOUS-209	gdgzegwgsg(lkkvgzymha) = wvzgjnlqbp kivtrvgkgb (oernqnklhs ) View more	Positive	26 May 2023
NCT04041310 (SITC2022) Manual	Phase 1	Turcot Syndrome First line Deficient DNA Mismatch Repair (dMMR) \| MSI-H	12	pembrolizumab+Nous-209 (dose level 1)	khnsmsutzm(lodatclwmz) = bzliijjxyc lsgqwfqptk (xlxcdyqqmb ) View more	Positive	27 Sep 2022
NCT04041310 (SITC2022) Manual	Phase 1		12	pembrolizumab+Nous-209 (dose level 2)	khnsmsutzm(lodatclwmz) = ouqfvibcdb lsgqwfqptk (xlxcdyqqmb ) View more	Positive	27 Sep 2022
AACR2022	Not Applicable	Microsatellite Instability cancer	-	Nous-209	zpymyymjtx(imqguaykei) = nguwjesqtq fbexmajhvu (wxscdklimk )	-	15 Jun 2022
NCT04041310 (ESMO2021) Manual	Phase 1	Turcot Syndrome Deficient DNA Mismatch Repair (dMMR) \| MSI	6	pembrolizumab+Nous-209	lkralwfakf(yspnhnevss) = None anvyoasidl (anoaqaysam )	Positive	16 Sep 2021

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