Foundation Medicine and Collaborators to Share Scientific Advances at AACR22 Reinforcing the Power of Genomic Testing in Precision Cancer Care

On April 5, 2022 Foundation Medicine, Inc. reported that the company and its collaborators will present a total of nine studies, including two clinical science symposia presentations and seven poster discussions, at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from April 8-13 (Press release, Foundation Medicine, APR 5, 2022, View Source [SID1234611468]).

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Highlights of these presentations include:

Two studies spotlighting the concordance between Foundation Medicine’s tissue and blood-based comprehensive genomic profiling (CGP) tests and their complementary value as tools to provide genomic insights to researchers and clinicians.
Data on Foundation Medicine’s new algorithm to predict homologous recombination deficiency (HRD) status and identify patients who may be candidates for PARP inhibitors across multiple disease types. Patient identification for PARP inhibitors remains a challenge, but these findings suggest that HRD status, including indel and copy number features, is associated with instability beyond ovarian cancer.
A new study leveraging existing data to identify 165 ancestry-associated features across multiple common cancer types. These findings help address the lack of knowledge about ancestry-specific alterations in an effort to overcome barriers to implementing precision medicine, including inequities in genetic testing, targeted treatment and clinical trial design for cancer patients from underserved populations.
"Data being presented at this year’s AACR (Free AACR Whitepaper) meeting emphasize our role as an essential partner for our collaborators who are working to identify patients most likely to benefit from new precision therapies," said Priti Hegde, PhD, chief scientific officer at Foundation Medicine. "Our research also highlights how the data derived from our portfolio of tests can shape the future of cancer care and research, including through our novel HRD algorithm."

The following is a list of abstracts that will be presented at the meeting. To access all abstracts being presented at AACR (Free AACR Whitepaper), please visit AACR (Free AACR Whitepaper).org.

Follow Foundation Medicine on Twitter and LinkedIn for more updates from #AACR22 and visit us in person at booth #2301.

Abstract #

Title

Collaborator

Product

Clinical Science Symposia

2139

Monday, April 11

2:35 PM – 2:50 PM

Evaluation of tissue- and plasma-derived tumor mutational burden and genomic alterations of interest from the CheckMate 848 clinical trial

Bristol Myers Squibb

Clinical trial assay based on FoundationOne CDx & Foundation Medicine bTMB Clinical Trial Assay

CT031

Monday, April 11

3:20 PM – 3:30 PM

TALAPRO-1: Talazoparib monotherapy in metastatic castration-resistant prostate cancer (mCRPC) with tumor DNA damage response alterations (DDRm)—Exploration of genomic loss of heterozygosity (gLOH) and potential associations with antitumor activity

Pfizer

Clinical trial assay based on FoundationOne CDx

Posters

57/18

Sunday, April 10

1:30 PM – 5:00 PM

Patients with germline ATM mutations develop clonal hematopoiesis characterized by co-occurrence of multiple somatic ATM alterations

FoundationCore

753/9

Monday, April 11

9:00 AM – 12:30 PM

Comprehensive genomic profiling (CGP) reveals site-specific enrichment of immunotherapy biomarkers and targetable alterations in non-small cell lung cancer (NSCLC) metastasis

FoundationCore

798/7

Monday, April 11

9:00 AM – 12:30 PM

Comprehensive genomic profiling of tissue and liquid biopsies reveals the landscape of reversion mutations

FoundationCore

1166/13

Monday, April 11

9:00 AM – 12:30 PM

Leveraging existing data to identify ancestry-associated features across multiple cancer types

Dana Farber Cancer Institute

FoundationCore

1243/15

Monday, April 11

9:00 AM – 12:30 PM

Identification of aneuploidy biomarkers associated with response to first-line treatment of metastatic pancreatic cancer

Foundation Medicine and Flatiron Health’s Clinicogenomic Database

1249/21

Monday, April 11

9:00 AM – 12:30 PM

Development of a pan-cancer algorithm to predict homologous recombination deficiency and sensitivity to PARPi therapy

University of Minnesota

Foundation Medicine and Flatiron Health’s Clinicogenomic Database & FoundationCore

3413/19

Tuesday, April 12

1:30 PM – 5:00 PM

Clinical utility of circulating tumor DNA sequencing with a large panel: The experience of Gustave Roussy/ National Center for Precision Medicine (PRISM)

Gustave Roussy Cancer Center

FoundationOne Liquid CDx

Good business performance gives Boehringer Ingelheim tailwind for investment in R&D

On April 5, 2022 Boehringer Ingelheim reported its annual investments in R&D to a new high in its 137-year history (Press release, Boehringer Ingelheim, APR 5, 2022, View Source [SID1234611466]). The company spent 4.1 billion EUR on R&D (2020: 3.7 billion EUR), up 11.7% . R&D investments in Human Pharma rose to 3.7 billion EUR (2020: 3.3 billion EUR), while investments in Animal Health were up 1% to 416 million EUR (2020: 412 million EUR).

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"2021 was a good year for patients, for animal owners and for our company. We expanded our contribution to transforming human and animal lives and further strengthened our combined pipeline," explained Hubertus von Baumbach, Chairman of the Board of Managing Directors. "Accordingly, we also intensified our efforts in Research and Development and achieved significant medical progress, including three breakthrough therapy designations granted by the US FDA for innovative medicines in Human Pharma. In Animal Health, we laid the foundation for the launch of innovative new solutions for companion animals and livestock in 2022 and 2023.

"We present these results at a time when war has been brought back to Europe," continued von Baumbach. "Our thoughts are with all Ukrainians. The aggression against the country is heartbreaking. We are supporting those seeking refuge and those in need in Ukraine, through short-term and long-term financial support, through product donations and supply of medicines, and many of our employees engage in support initiatives using our volunteering days program. We all hope that this horrific situation will end soon."

Growth across all businesses

Despite the ongoing COVID-19 challenges, 2021 was a successful year. Boehringer Ingelheim recorded net sales of 20.6 billion EUR (2020: 19.6 billion EUR), a 5.4% increase compared to the previous year. Adjusted for currency effects, net sales rose by 7.5%.

Operating income at Group level rose to 4.7 billion EUR (2020: 4.6 billion EUR). Income after taxes saw an 11.2% year-on-year increase to 3.4 billion EUR (2020: 3.1 billion EUR). Cash flow from operating activities decreased slightly by 117 million EUR to 3.9 billion EUR (2020: 4.0 billion EUR). At the end of 2021, the equity ratio stood at 48% (2020: 47%).

"All our businesses contributed to the solid financial results in 2021, a strong achievement, especially when considering the overall pandemic and economic situation. As a result, we can continue making significant investments and have strengthened our overall financial basis – and thus our independence," said Michael Schmelmer, Member of the Board of Managing Directors responsible for Finance and Group Functions. "The extraordinary commitment of all our employees in a second pandemic year drove our achievements. Working conditions were often challenging, both for those of us who worked from home on an almost permanent basis and for those who worked under restricted conditions on our sites. In times of need, we all stand up for each other. This makes me feel positive and optimistic and is particularly important for the long-term success of our company."

Human Pharma – Significant progress in late-stage R&D pipeline

The R&D pipeline in Human Pharma comprises more than 100 clinical and preclinical projects. Based on the progress of the later stage projects, the pipeline has the potential to deliver up to 15 new product launches until 2025. A key focus in research is to gain a deeper understanding of the connections between different diseases. JARDIANCE (empagliflozin) is a good example. This medication was initially approved as a type 2 diabetes medication. Investing into the better scientific understanding of the interconnectedness of cardio, renal and metabolic systems has enabled Boehringer Ingelheim to broaden its use from diabetes to heart failure. Empagliflozin is now the only approved treatment for adults with symptomatic chronic heart failure in the European Union. Furthermore, it may also be of benefit in a broad range of chronic kidney diseases, as demonstrated from a positive interim analysis data readout of the EMPA-KIDNEY trial. It is also being assessed for the prevention of heart failure following a heart attack in the ongoing EMPACT-MI trial.

The pace of innovation from the company’s immunology research was further underscored by Spesolimab, an IL-36 specific monoclonal antibody for the treatment of generalized pustular psoriasis (GPP). GPP is a rare and sometimes even life-threatening skin disease with no globally approved treatments. Spesolimab has been granted US FDA Breakthrough Therapy Designation and pivotal data was published in the New England Journal of Medicine. Regulatory submissions for the treatment of GPP flares have been filed in major geographies, with the aim of bringing Spesolimab to eligible patients this year.

Other inflection points for the company’s R&D pipeline this year include lung fibrosis, the central nervous system (CNS) and oncology. A study to evaluate how a PDE4B inhibitor affects lung function of people with idiopathic pulmonary fibrosis (IPF) will be published at a medical conference later this year. In February 2022, the US FDA has granted Breakthrough Therapy Designation to the compound in this indication. In CNS, a Gly-T1 inhibitor was also granted US FDA Breakthrough Therapy Designation for the treatment of Cognitive Impairment Associated with Schizophrenia (CIAS), and a high level data readout is anticipated for later this year. Also in CNS, Boehringer Ingelheim is collaborating on the digital therapeutic CT-155 as an adjunct to pharmacotherapy, which aims to help patients modify their behavior and train new skills. The promising MDM2-p53 antagonist is the most advanced asset in oncology now in a pivotal phase II clinical trial for rare soft tissue sarcoma, an area of significant unmet medical need that lacks novel approved therapies.

Strong growth for JARDIANCE and OFEV

At 15.3 billion EUR (2020: 14.4 billion EUR), net sales of human pharmaceuticals grew by 8.4%* and accounted for 74% of total net sales. The United States remains the largest market for Boehringer Ingelheim. The company generated net sales of 5.8 billion EUR (2020: 5.7 billion EUR) in the US, up 5.9%*. In the EUCAN region (Europe, Canada, Australia, and New Zealand, net sales excluding licensing income) rose by 4.1%* to 4.4 billion EUR (2020: 4.2 billion EUR). In Emerging Markets, including the People’s Republic of China, the company registered net sales of 3.0 billion EUR (2020: 2.8 billion EUR), a 5.9%* increase. In Japan, net sales increased by 7.1%* to 1.3 billion EUR (2020: 1.3 billion EUR).

Medicines for the treatment of cardiovascular and metabolic, as well as respiratory diseases, remain the most important contributors to net sales. JARDIANCE remains the biggest revenue contributor in Human Pharma, generating net sales of 3.9 billion EUR (2020: 3.1 billion EUR) and growth of 28.6%*. OFEV was the company’s second-strongest revenue contributor with net sales of 2.5 billion EUR (2020: 2.1 billion EUR) and growth of 25.4%*.

Animal Health – Higher net sales in a very competitive market

The Animal Health business of Boehringer Ingelheim is a global leading provider of vaccines, therapeutics and preventative care offerings that protect animals from disease and pain. In 2021, the Animal Health business significantly increased its net sales in a highly competitive market and grew by 6.2%*, with net sales of 4.3 billion EUR (2020: 4.1 billion EUR).

In terms of sales, the companion animals’ portfolio remains by far the largest segment of Boehringer Ingelheim Animal Health, including the best-selling product NEXGARD, a parasiticide for dogs, with growth of 16.6%* and net sales of 916 million EUR (2020: 804 million EUR). The antiparasitic FRONTLINE for dogs and cats is another major product, with net sales up 4.8%* at 418 million EUR (2020: 406 million EUR). Growth in this segment was also fueled by more people acquiring a new pet during the COVID-19 pandemic.

The livestock segment grew only moderately due to the ongoing COVID-19 pandemic and African swine fever, especially in Asia and Europe. Whereas the overall swine segment expanded by 3%, the swine vaccine INGELVAC CIRCOFLEX saw a decline in sales of -2.7%* to 253 million EUR (2020: 264 million EUR).

Biopharmaceutical production – One of the leading providers in the industry

Boehringer Ingelheim is one of the leading manufacturers of biopharmaceuticals, both for its own portfolio and for partners in the industry. 60% of the top 20 pharmaceutical companies and innovative biotech firms are clients of Boehringer Ingelheim’s Biopharmaceutical Contract Manufacturing business, known under the brand name Boehringer Ingelheim BioXcellenceTM. The biopharmaceuticals business achieved net sales of 917 million EUR in 2021 (2020: 837 million EUR), up 9.5%* due to strong demand for our customers’ products.

Investments in tangible fixed assets remain at a high level

In 2021, the company invested 968 million EUR (2020: 1.05 billion EUR) in tangible fixed assets, including the large-scale production facility for biopharmaceutical products (LSCC) in Vienna, Austria, which was inaugurated in October 2021, and the new development center for biopharmaceutical medicines (BDC) in Biberach, Germany. Restricted construction activities due to the COVID-19 pandemic had an impact on the investment sum.

Outlook for 2022: Boehringer Ingelheim expects a slight year-on-year increase in net sales on a comparable basis

The ongoing COVID-19 pandemic, the geopolitical tensions in Europe and a challenging industry environment are expected to have an impact on the results of Boehringer Ingelheim. For 2022, the company expects to achieve a slight year-on-year increase in net sales on a comparable basis. For the next five years, plans are to invest over 25 billion EUR in its research pipeline. In addition, capital expenditures for novel production technologies and a cutting-edge supply network are planned, with well over 7 billion EUR of investments targeted for the next five years. This includes further expansion of the biopharmaceutical production capacities.

*year on year and adjusted for currency effects

2021 Annual Report at View Source

Please click on the link for "Notes to Editors" and "References"

View Source

Agenus’ CD137 Agonist (AGEN2373) Advances in the Clinic, Triggering Milestone Payment from Gilead

On April 5, 2022 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of therapeutics designed to activate immune response to cancers and infections, reported receipt of a $5M clinical milestone payment for AGEN2373 (conditionally active CD137 agonist) (Press release, Agenus, APR 5, 2022, View Source [SID1234611464]). AGEN2373 is being evaluated in a Phase 1b combination study with botensilimab (Fc-enhanced anti-CTLA-4), in melanoma patients who had relapsed on, or were refractory to, prior anti-PD-1 therapy.

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"The majority of patients treated with anti-PD-1 progress within a year and are in need of more effective treatment options," said Steven O’Day, MD, Chief Medical Officer of Agenus. "Botensilimab has shown promising activity in a wide range of treatment-resistant cancers, including melanoma. The rationale to combine botensilimab and AGEN2373 is based on preclinical evidence we reported of enhanced tumor control with this approach in a PD-1 resistant melanoma model. This study represents a rationally designed combination strategy to bring novel therapies to cancer patients."

AGEN2373 has demonstrated preliminary clinical benefit and has been well tolerated without signs of liver toxicity, an adverse event that has impacted competitor antibodies in the clinic. Gilead currently has an exclusive option to license AGEN2373. Agenus retains the right to opt-in to share Gilead’s development and commercialization costs in the United States in exchange for a 50:50 profit share and US co-commercialization rights.

References

A. Tolcher et al., Initial findings of the first-in-human Phase I study of AGEN2373, a conditionally active CD137 agonist antibody, in patients (pts) with advanced solid tumors. Presented at the ASCO (Free ASCO Whitepaper) 2021 Virtual Meeting.

C. Galand et al., AGEN2373 is a CD137 agonist antibody designed to leverage optimal CD137 and FcγR co-targeting to promote antitumor immunologic effects. Presented at the SITC (Free SITC Whitepaper) 2020 Virtual Meeting.

About AGEN2373
AGEN2373 is a fully human monoclonal antibody designed to boost the immune response to cancer cells by enhancing CD137 co-stimulatory signaling in activated immune cells. The unique binding properties of AGEN2373 are expected to limit its activity outside of the tumor site and mitigate toxicities that may be associated with systemic activation of CD137 in humans.

About Botensilimab
Botensilimab (also known as AGEN1181) is a next-generation, Fc-enhanced, immunoglobulin G1 (IgG1) antibody designed to block CTLA-4 (cytotoxic T-lymphocyte associated antigen 4) inhibitory function from interacting with its ligands CD80 and CD86. The Fc region of the antibody was engineered to enhance immune activation and tumor killing, improve safety, and benefit a broader patient population versus first-generation anti CTLA-4 antibodies. CTLA-4 is a negative regulator of immune activation that is considered a foundational target within the immuno-oncology market.

Mersana Therapeutics to Present Preclinical Data on XMT-1660, XMT-2056 and the Immunosynthen Platform at AACR Annual Meeting

On April 5, 2022 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that it will present three posters highlighting data for XMT-1660, XMT-2056, and the Immunosynthen ADC platform at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 to be held in New Orleans, Louisiana from April 8-13, 2022 (Press release, Mersana Therapeutics, APR 5, 2022, View Source [SID1234611463]).

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"ADC innovation is at the core of Mersana’s strategy, and we have made significant progress in building out an innovative pipeline of potential cancer medicines. Our preclinical data show the potential of XMT-1660 in a range of B7-H4 expressing tumors and the power of our Dolasynthen platform," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "The preclinical profile of XMT-2056 as monotherapy and in combination with standard of care therapies in both HER2-high and HER2-low expressing models reinforces the differentiation of the Immunosynthen platform. We look forward to advancing both molecules into the clinic in mid-2022."

XMT-1660 is a Dolasynthen ADC targeting B7-H4, a target selectively expressed on tumors in areas of high unmet medical need, including breast, endometrial, ovarian and other cancers. The data show that a single dose of XMT-1660 has anti-tumor activity in both triple-negative breast cancer (TNBC) and estrogen receptor (ER)-positive breast cancer xenograph models. Higher B7-H4 expression is associated with greater anti-tumor activity of XMT-1660 in preclinical studies. Mersana expects a Phase 1 clinical trial for XMT-1660 to start in mid-2022.

XMT-2056, Mersana’s first Immunosynthen STING-agonist ADC, targets a novel epitope of HER2, and is designed to offer a differentiated and complementary therapeutic approach to the treatment of HER2-expressing tumors. The preclinical data presented show that XMT-2056 demonstrates robust anti-tumor activity as a monotherapy in both HER2-high and HER2-low expressing models. XMT-2056’s complementary mechanism of action results in increased efficacy in combination with trastuzumab, pertuzumab, anti-PD-1, or trastuzumab deruxtecan in preclinical studies. Mersana expects to initiate a Phase 1 clinical trial of XMT-2056 in mid-2022.

Immunosynthen is Mersana’s immunostimulatory ADC platform designed to take ADCs beyond traditional cytotoxic drugs to targeted stimulation of the innate immune system. Data show that anti-tumor activity of Immunosynthen STING-agonist ADCs involves the targeted activation of the STING pathway in an antigen binding-dependent manner in both tumor-resident immune cells and in tumor cells. In addition to delivery to the tumor cell via antigen binding and internalization, data from multiple models demonstrate Fcγ-R1 is the major receptor that mediates delivery to a specific population of myeloid cells resident in primary human tumors, eliciting potent anti-tumor responses in preclinical studies.

Details of the presentations are as follows:

Poster Title: Anti-tumor effect of XMT-1660, a B7-H4 targeting antibody drug conjugate, in an unselected panel of patient derived xenograft models of breast cancer
Poster Board Number: 8
Session Category: Experimental and Molecular Therapeutics
Session Title: Antibody Drug Conjugates
Date/Time: Monday, April 11, 2022 at 1:30pm – 5:00pm CDT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 21

Poster Title: XMT-2056, a HER2-targeted Immunosynthen STING-agonist antibody-drug conjugate, binds a novel epitope of HER2 and shows increased anti-tumor activity in combination with trastuzumab and pertuzumab
Poster Board Number: 5
Session Category: Immunology
Session Title: Immunomodulatory Agents and Interventions 2
Date/Time: Tuesday, April 12, 2022 at 1:30pm – 5:00pm CDT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 37

Poster Title: Tumor cell-targeted STING-agonist antibody-drug conjugates achieve potential anti-tumor activity by delivering STING agonist specifically to tumor cells and FcγRI-expressing subset of myeloid cells
Poster Board Number: 15
Session Category: Immunology
Session Title: Innate Immunity to Cancer
Date/Time: Monday, April 11, 2022 at 1:30pm – 5:00pm CDT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 40

Oncorus Announces Debt Capital Facility with K2 HealthVentures with $20 Million Funded at Closing, Relocation of Corporate Headquarters and Extension of Cash Runway

On April 5, 2022 Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapies company focused on driving innovation to transform outcomes for cancer patients, reported that it has entered into a loan and security agreement with K2 HealthVentures (K2HV), a healthcare focused specialty finance company (Press release, Oncorus, APR 5, 2022, View Source [SID1234611462]). Also today, Oncorus announced plans to relocate all its operations to its facility in Andover, Massachusetts in the fourth quarter of 2022, to allow research, process development and Good Manufacturing Practice (GMP)-compliant manufacturing to occur all in one facility. As a result of the term loan facility and operations relocation, as well as other initiatives to increase operational efficiency, Oncorus now expects its cash, cash equivalents and investments to fund its capital expenditures and operating expenses into early 2024.

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The term loan facility provides Oncorus with up to $45 million available in multiple tranches upon the achievement of certain time-based, clinical and regulatory milestones with the initial tranche of $20 million funded at closing. Oncorus intends to use the proceeds of the initial tranche of the loan facility to complete the buildout of its Andover facility, and to continue the advancement of its pipeline of next generation viral immunotherapies for cancer and lipid nanoparticle (LNP) technologies, including the filing of an investigational new drug application (IND) for its intravenously administered vRNA/LNP product candidate, ONCR-021, planned for mid-2023.

"Access to this additional capital from our partners at K2HV provides us with resources to aggressively pursue our strategic operational and manufacturing priorities, including the completion of construction of our manufacturing facility in Andover. This facility will play an integral role in helping us to rapidly advance our next generation viral immunotherapies for cancer patients derived from our HSV and selectively self-amplifying viral RNA (vRNA) platforms," said Ted Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. "Coupled with this additional capital comes our decision to move all operations to our Andover facility by the fourth quarter of this year, providing us with increased synergies for our continued rapid growth and innovation, while extending our current cash runway into 2024. We are incredibly pleased to partner with the K2HV team and value their significant experience supporting successful biotechnology companies."

"We are excited to partner with Oncorus as they continue to build out their state-of-the-art manufacturing infrastructure and advance their dual-platform pipeline of product candidates targeting cancers with significant unmet need," added Anup Arora, Founding Managing Director & Chief Investment Officer at K2HV. "This financing is in line with our strategy of investing in innovative life sciences companies whose goals are to help improve outcomes for patients. We look forward to working with the Oncorus team and supporting their vision."

"The move to our Andover facility marks a significant turning point for Oncorus as we continue to work towards becoming a fully integrated leader in viral immunotherapies for cancer and LNP technologies," said Stephen W. Harbin, Chief Operating Officer and Chief of Staff of Oncorus. "By bringing our research, process development and GMP manufacturing teams to the same facility, we believe that we will be better positioned for rapid success while also providing an opportunity for strong collaboration and efficiency as we collectively work to achieve our milestones. The continued investment in manufacturing and building out our in-house LNP capabilities reflects our commitment to innovation and the value of our infrastructure."

Further information with respect to the loan and security agreement will be set forth in a Current Report on Form 8-K to be filed by Oncorus with the Securities and Exchange Commission on April 5, 2022.