Novartis has agreed to acquire Mariana Oncology for up to $1.75 billion, the companies said today, in a deal that would further expand the buyer’s radiopharmaceutical and cancer pipelines, research infrastructure, and clinical supply capabilities.

Based in Watertown, MA, Mariana has built a pipeline of preclinical radioligand therapies (RLTs) ranging from lead optimization to early development phases, designed to treat cancers deemed to have high unmet need. Mariana’s RLTs—which combine a tumor-targeting ligand with a therapeutic radioisotope—are designed to bind to specific receptors expressed on the surface of tumors.

Mariana’s pipeline encompasses solid tumor indications such as breast, prostate, and lung cancer. The company’s lead candidate, MC-339, is an actinium-based peptidic small molecule designed to treat small cell lung cancer (SCLC) by targeting an undisclosed target.

“Our strategy has centered on overcoming the unique challenges of end-to-end radiopharmaceutical R&D and ultimately, delivery of these drugs to the bedside,” Simon Read, PhD, Mariana’s founder and CEO, said in a statement. “Both Mariana and Novartis are committed to transforming cancer care, and together we will be in a better position to do that.”

Novartis has two approved RLTs:

  • Pluvicto® (lutetium Lu 177 vipivotide tetraxetan), indicated for adults with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.
  • Lutathera® (lutetium Lu 177 dotatate), a radiolabeled somatostatin analog indicated for adults and adolescents ages 12 and older with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors.

Novartis RLT Pipeline

Under the name AAA601, Lutathera is also in Phase III development for first-line treatment of G2/3 GEP-NET tumors, and Phase II development for first-line extensive-stage SCLC, GEP-NET tumors in children, and glioblastoma. And under the name AAA617, Pluvicto is in Phase III for oligometastatic prostate cancer, metastatic hormone sensitive prostate cancer (mHSPC), and metastatic castration-resistant prostate cancer (mCRPC) pre-taxane.

Novartis has several additional RLTs in or entering the clinic, including:

  • AAA603 (177Lu-NeoB), which is in Phase I for glioblastoma multiforme, breast cancer, and multiple solid tumors.
  • AAA604, a Phase I candidate for pancreatic cancer.
  • AAA614, a Phase I candidate for solid tumors.
  • AAA802 (225Ac-PSMA-R2), another Phase I prostate cancer candidate, and
  • AAA817 (225Ac-PSMA-617), a Phase I candidate for mCRPC.

The pharma giant added that it is actively looking at new disease areas for RLTs, as well as exploring new isotopes and new combinations with complementary mechanisms of action.

“The acquisition of Mariana Oncology reflects our commitment to radioligand therapy as one of our company’s key technology platforms and strengthens our leadership in this field,” stated Fiona Marshall, PhD, president of biomedical research at Novartis. “We are excited to work with the Mariana team to bring forward next-generation RLTs for patients living with cancer and together shape the future of RLT as a pillar for oncology treatment.”

At least one analyst shared Novartis’ enthusiasm for the Mariana acquisition.

Growing appetite

Andrew Tsai, an equity research analyst with Jefferies, wrote today in a research note that Novartis’ planned purchase of Mariana “suggests Big Pharma not only (1) is willing to explore more modalities (peptides), newer isotopes (225Ac) and other $1B+ cancer targets (SCLC lung), but also (2) has appetite for earlier-stage preclinical platforms. Nonetheless, the acquisition should benefit all players in the space.”

“We expect radiopharma to remain a major theme in 2024–25,” Tsai added.

Novartis agreed to pay Mariana $1 billion upfront and up to an additional $750 million tied to achieving milestones. The deal is subject to customary closing conditions.

Novartis shares started today declining about one percent from yesterday’s close of $97.50 to $96.85 at 9:48 a.m., before inching back to $97.25 as of 10:40 a.m.

Privately held Mariana was founded in 2021 by Atlas Venture, Access Biotechnology and RA Capital Management. Last September, Mariana closed on an oversubscribed $175 million Series B financing whose proceeds were intended to support the advancement of the company’s RLTs, including MC-339.

Deep Track Capital and Forbion co-led the financing, joined by new investors that included Nextech Invest, Surveyor Capital (a Citadel company)—and Eli Lilly, which expanded into radiopharmaceutical development last year, when it acquired Point Biopharma Global for approximately $1.4 billion in a deal completed in December 2023.

At the time of the Series B financing, Mariana said it expected to enter the clinic with MC-339 in 2024 using its own Good Manufacturing practice (GMP) manufacturing.

“This acquisition of Mariana Oncology brings to Novartis phenomenal talent and new capabilities in radioligand therapeutic research that complement our wide-ranging internal research and drug discovery efforts, in addition to our translational and clinical development capabilities,” added Shiva Malek, PhD, global head of oncology for biomedical research at Novartis. “This is an ideal pairing, and we are thrilled to continue to do pioneering science together, translating RLT discovery into clinical development to deliver transformative therapies to patients.”

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