Atezolizumab

Tempest ended the 2024 fiscal year with $30.3m in cash, down from $39.2m at the end of 2023. Image credit: Shutterstock / Andrii Yalanskyi. Tempest Therapeutics is charting rocky waters as it looks to secure a partner to advance its liver cancer drug through a Phase III trial. The US biotech’s clinical asset, amezalpat, has already demonstrated positive Phase II data, though the step to Phase III looks more difficult. “The capital markets have been unavailable to support the next stage of development,” Tempest’s CEO Stephen Brady said in a statement. The company is looking at “strategic alternatives”, which could include a merger, acquisition, or partnership. Joint ventures, licensing arrangements, and other transaction types are also on the table. Brady added that the options “include finding a strategic partner with the resources to develop what we believe are potentially life-saving therapies for patients in need”. Tempest made the announcement after market close on 9 April after its Nasdaq-listed shares closed 10.7% higher, in part due to a stock split executed by Tempest on the same day. The biotech has a market cap of $25.1m. Investment in biotech and biopharma has been at an all-time low since the 2021 boom . This has made it difficult for companies to advance therapies through trials without seeking alternative funding methods. Amezalpat, dubbed TPST-1120, has the US Food and Drug Administration (FDA) go-ahead for a pivotal Phase III trial (NCT06680258). The orally administered drug will be evaluated in combination with Roche’s Tecentriq (atezolizumab) and Genentech’s Avastin (bevacizumab) in unresectable or metastatic hepatocellular carcinoma (HCC). Tempest secured the services of Roche to supply Tecentriq for the planned trial via an October 2024 partnership. The two companies were already collaborating on a Phase I/II umbrella study (NCT04524871) evaluating amezalpat in combination with Tecentriq and Avastin in first-line HCC patients and compared to Tecentriq and Avastin alone. Amezalpat demonstrated a six-month improvement in median overall survival (OS) for patients receiving the combination therapy, in comparison to the control arm of Roche’s and Genentech’s treatments alone. Amezalpat is a peroxisome proliferator-activated receptor alpha (PPAR⍺) antagonist. PPAR⍺ is a nuclear receptor involved in lipid metabolism pathways, though growing evidence suggests it can also modulate carcinogenesis. Despite growing competition in the liver cancer treatment space, revenue for drugs remains high. Tecentriq generated sales of $2.14bn for Roche in 2024, making it one of the big pharma’s top-selling drugs. Tempest believes that amezalpat can join the high-revenue party, stating that it holds blockbuster potential in first-line HCC. There are no PPAR⍺ antagonists currently approved by the FDA. The agency has noted the drug’s promise, granting it fast track designation and orphan drug designation for the treatment of HCC. Tempest’s pipeline also includes a dual EP2/4 prostaglandin receptor antagonist named TPST-1495. The biotech is also seeking the same strategic partnerships for a Phase II study of this asset.  TPST-1495 has FDA orphan drug designation for the treatment of familial adenomatous polyposis (FAP). Tempest ended the 2024 fiscal year with $30.3m in cash, down from $39.2m at the end of 2023. Loss for the biotech increased from $29.5m in 2023 to $41.8m in 2024.

iStock, invincible_bulldog According to Tempest, its options include a partnership or licensing deal, as well as a merger or an acquisition. Tempest Therapeutics is looking for “strategic alternatives” that will allow it to take its investigational PPARα antagonist amezalpat forward into late-stage development, the biotech announced on Thursday. Some of Tempest’s options include searching for a partner, licensing deals or joint ventures over amezalpat. The company is also open to a merger or an acquisition, as per its news release. Tempest has not provided a timeline for this strategic review, nor did it make any promises that Thursday’s announcement will result in a business transaction. Tempest’s scramble for funding isn’t surprising. In a March 27 note to investors, William Blair analysts noted that the biotech had just over $30 million in cash and cash equivalents—only enough to cover the “start-up costs” of a Phase III trial for amezalpat. Tempest already has a partner for amezalpat—and a powerhouse one at that. In October 2024, the California-based biotech inked a collaboration agreement with Roche to study amezalpat in combination with Tecentriq and bevacizumab (marketed by Roche under the brand name Avastin), positioning the regimen as a frontline option for unresectable or metastatic hepatocellular carcinoma (HCC). Roche has committed to providing a supply of Tecentriq for the trial, while Tempest will remain the study’s principal sponsor. That 2024 deal is a follow-up to a 2021 collaboration on the same drug combos in a Phase Ib/II trial . Tempest retains all development and commercial rights to amezalpat. “Clearly additional funding will be needed to fully conduct the Phase III study,” the William Blair analysts noted, “which we believe could come from an additional development partner and/or equity financing.” Still, William Blair expressed optimism about Tempest and amezalpat, which it called “an attractive development opportunity for multiple partners.” Designed to be taken orally, amezalpat is a small-molecule drug that selectively binds to and blocks PPARα, a transcription factor protein involved in various lipid-related metabolic processes. Tempest is studying amezalpat for HCC, a cancer of the liver that some studies have linked to sustained and excessive PPARα activation. In June 2024, Tempest released Phase Ib/II data for the drug, showing that when used with Tecentriq and bevacizumab, the oral PPARα blocker elicited a 35% improvement in overall survival (OS) versus Tecentriq plus bevacizumab alone. Patients given the amezalpat regimen saw median OS of 21 months as compared to 15 months in control comparators. In its news release on Thursday, Tempest also revealed that it had already completed an end-of-Phase II meeting with the FDA and has aligned with the regulator on a Phase III study for the amezalpat combo regimen.