Moderna, Inc., (Nasdaq: MRNA) a clinical-stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced interim data from an ongoing Phase 1 clinical study of mRNA-2752 (Triplet) in patients with accessible solid tumors and lymphomas. The data showed that the Company’s mRNA Triplet program given in combination with AstraZeneca’s durvalumab (IMFINZI®) was tolerated at all dose levels tested and elicited evidence of anti-tumor activity. The recommended dose for expansion (RDE) is up to of 8mg mRNA-2752 + durvalumab.

“We are encouraged by the interim data from our Triplet program, which combines three mRNAs into one therapy injected directly into the tumor. Our intratumoral mRNA technology allows for the delivery of mRNAs encoding for multiple proteins that act locally to modulate the tumor microenvironment, without systemic toxicity,” said Praveen Aanur, M.D., Vice President, Therapeutic Area Head for Oncology Development at Moderna. “These interim results demonstrate the potential role of immune modulation on clinical outcomes and we look forward to full results from the dose expansion arm of the study.”

Presented today at the Society for Immunotherapy of Cancer's (SITC) 36th Annual Meeting, the study demonstrates evidence of immunomodulation and expected pharmacodynamics in the tumour immune microenvironment (TME) of both injected and un-injected lesions, in both monotherapy and combination cases, as indicated by increases in proliferating (activated) T cells, PD-L1 levels (marker of interferon signaling), and T cell-inflamed (GEP) and DC transcriptional signature score, with greatest changes observed in patients with clinical benefit.

This Phase 1 open-label, multicenter, dose-escalation study is evaluating the safety and tolerability of escalating intratumoral injections of mRNA-2752 alone and in combination with PD-L1 inhibitor (durvalumab) to define the maximum tolerated dose (MTD) or a recommended dose for expansion (RDE). The study consists of dose escalation and dose confirmation parts, which will occur in Arm A and Arm B, followed by a dose expansion part, which will occur in Arm B, and a Dose Exploration in Arm C as a neoadjuvant therapy for cutaneous melanoma. The Company presented the interim results of Part A at the 2020 ASCO Annual Meeting. Enrollment in dose expansion part of Arm B and Arm C is currently ongoing.

Moderna's mRNA technology enables novel combination of targets. mRNA-2752 consists of three mRNAs which encode for different proteins including OX40 ligand, a T-cell costimulatory protein, which can enhance expansion and survival of both CD4 and CD8 T cells; and two cytokines, IL-23, a pro-inflammatory cytokine of the IL-12 family, which can cause priming of dendritic cells and also activation of other immune cells; and IL-36γ, a pro-inflammatory cytokine of IL-1 family, which can help in the maturation of dendritic cells.

About the Data

Abstract 529: Phase 1 Study of mRNA-2752, a Lipid Nanoparticle Encapsulating mRNAs Encoding huOX40L, IL-23, and IL-36γ Intratumoral (iTu) Injection +/- Durvalumab in Advanced Solid Tumors and Lymphoma

The SITC poster is now available on the "Events and Presentations" section of the Moderna website.

In Arm B of this dose-escalation study, 32 patients with accessible solid tumors and lymphomas received mRNA-2752 in combination with intravenously administered immune checkpoint blockade therapy (durvalumab).

Results:

• iTu mRNA-2752 given as monotherapy and in combination with durvalumab is tolerable at all dose levels studied; the recommended dose for expansion (RDE) is up to 8mg mRNA-2752 + durvalumab
  
  
  
  
• Median IL-23 plasma levels maintained at < 1ng/mL with dose ranges up to 8mg supports the therapeutic goal of ITu therapy to limit systemic exposure and toxicity
  
  
  
  
• Administration of iTu mRNA-2752 is associated with tumor shrinkage in both injected and un-injected lesions as monotherapy and in combination with durvalumab
  
  
  
  
• Durable PRs seen in a PD-L1-low squamous-cell bladder cancer patient, and a Diffuse large B-cell lymphoma (DLBCL) after progression on CAR-T
  
  
  
  
• Treatment response of the injected lesion was seen in a melanoma patient progressed on pembrolizumab and T-VEC
  
  
  
  
• Evidence of immunomodulation/ expected pharmacodynamics in the TME of both injected and un-injected lesions, in both monotherapy and combination cases, as indicated by increases in proliferating (activated) T cells, PD-L1 levels (marker of interferon signaling), and T cell-inflamed (GEP) and DC transcriptional signature score, with greatest changes observed in patients with clinical benefit
  
  
  
  
• Pro-inflammatory cytokines, including IFN-γ, are predominantly transiently elevated post- monotherapy treatment, peaking at 24 hours post-treatment; trend toward further elevated levels of a subset of cytokines, including TNF-α, in combination with durvalumab
  
  
  
  
• PK/PD modeling supports QW dosing which is being explored in cutaneous melanoma in the neoadjuvant setting
  
  
  
  
• Enrollment is ongoing in expansion cohorts of triple-negative breast cancer (TNBC), urothelial carcinoma, lymphoma, and immune checkpoint refractory melanoma and n on-small cell lung cancer (NSCLC)

About Moderna’s Immuno-Oncology Programs

Moderna’s oncology programs are currently focused on two main areas: cancer vaccines and intratumoral immuno-oncology (I/O) therapies. Moderna is developing these potential mRNA treatments as monotherapies and/or in combination with checkpoint inhibitors from our strategic collaborators Merck and AstraZeneca.

An advantage of Moderna’s mRNA platform is that it allows for investigational medicines that combine in a single mRNA therapy several different approaches to activate the immune system to attack cancer, either with mRNA encoding for common tumor proteins found across cancer types or multiple mRNAs encoding for various immunomodulatory proteins.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including regarding: the Company’s development of its mRNA Triplet program (mRNA-2752); the tolerability of mRNA-2752 when administered in combination with AstraZeneca’s durvalumab and its ability to elicit anti-tumor activity; the conduct of clinical trials for mRNA-2752; and the potential advantages of the Company’s mRNA platform for developing cancer treatments. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna’s control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include those other risks and uncertainties described under the heading “Risk Factors” in Moderna’s most recent Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) and in subsequent filings made by Moderna with the SEC, which are available on the SEC’s website at www.sec.gov. Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna’s current expectations and speak only as of the date hereof.

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