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JP Morgan Healthcare Conference, Day 2: Roche, Zai Lab, Revolution Medicines, Ideaya Biosciences

JPMorgan23 grand ballroom

SAN FRANCISCO – The 41st Annual JP Morgan Healthcare Conference continued with more firms providing business updates and discussing development plans for precision oncology drugs and tests. 

Below are brief reports on individual presentations from the conference on Tuesday. A recap of Day 1's news is available here


Roche CFO Alan Hippe said that in 2023 the Swiss biotech expects to lose roughly $5 billion, representing around 8 percent of total sales, in COVID-19 related product revenue compared to 2022. The company also expects continued revenue losses for three former top-selling oncology drugs, Herceptin (trastuzumab), Avastin (bevacizumab), and Rituxan (rituximab), which face generic competition. In 2022, Roche lost $2 billion in sales of these drugs compared to 2021, and while losses in 2023 will be less year over year, they'll still be "significant," Hippe predicted. 

"We're expecting the underlying business and the base business in pharma and diagnostics to grow rather well," Hippe said, acknowledging that "it will be very, very hard to grow sales in 2023." 

Despite tough macroeconomic conditions, the firm has an overarching goal to double the number of patients using its drugs in lower- and middle-income countries by 2026 and double the number of patients with access to its diagnostics solutions by 2030. Roche's ongoing efforts to develop innovative products in its oncology franchise will contribute to these goals. 

For example, the company is developing its own KRAS G12C inhibitor, dubbed RG6330, which is currently being investigated as a second-line treatment for non-small cell lung cancer in a Phase III trial. This agent would likely compete with marketed KRAS inhibitors: Amgen's Lumakras (sotorasib) and Mirati's Krazati (adagrasib). And despite the SERD giredestrant, under development for estrogen receptor-positive HER2-negative advanced breast cancer, failing to meet its primary endpoint in an all-comer population in the Phase II acelERA trial last year, the drug appears to benefit those with ESR1 mutations. As such, Roche is continuing to study the drug in a Phase III trial in hormone receptor-positive breast cancer. 

The company's position on its anti-TIGIT immunotherapy tiragolumab still hasn't changed. Last year, the combination of tiragolumab plus the PD-L1 inhibitor Tecentriq (atezolizumab) failed to significantly improve progression-free survival compared to just Tecentriq in PD-L1-high advanced NSCLC patients. But since patients in the combination arm of the SKYSCRAPER-01 trial had numerically higher overall survival, Roche decided to continue the study until this co-primary endpoint matures. The next overall survival interim analysis is slated to read out later this month or in February, and the final analysis will be reported six months later. 

Gilead Sciences recently reported that the combination of its anti-TIGIT therapy domvanalimab plus the PD-1 inhibitor zimberelimab benefits PD-L1-high advanced NSCLC patients. This gives Roche added confidence regarding tiragolumab's eventual success, Hippe reflected. "We remain very confident on tiragolumab," he said. "The Gilead readout is supportive … that there is efficacy for the PD-1/PD-L1 and TIGIT combination in first-line non-small cell lung cancer." 

Zai Lab 

Shanghai-based Zai Lab has agreements to co-develop and -commercialize precision cancer drugs with the likes of Seagen, Mirati, Turning Point Therapeutics, Novocure, and GlaxoSmithKline, under which Zai Lab maintains rights in China while the partners hold rights in other markets. The company wants to continue to ink such agreements in 2023, according to Zai Lab CEO Samantha Du, and further solidify its position as the "partner of choice" for drug companies looking to commercialize their products in China. 

For instance, Zai Lab has the rights to commercialize Turning Point Therapeutics' ROS1/TRK/ALK inhibitor repotrectinib for certain non-small cell lung cancer patients in China. Bristol Myers Squibb last year acquired Turning Point Therapeutics and is expecting regulatory approval for repotrectinib in treatment-naïve, ROS1-positive NSCLC patients during the second half of 2023. 

Du said the firm is also going to focus this year on global business development opportunities, both with partners and emerging from its internal precision oncology pipeline. The firm's internal pipeline features drugs targeting DNA-dependent protein kinases, such as CCR8, Claudin18.2 in gastric cancer patients, and others. Zai Lab is also developing a novel DNA damage response-targeting program in partnership with Schrödinger. 

Zai Lab is optimistic that the reimbursement environment for its drugs will improve as the proportion of commercially insured patients increases in China. By 2025, Du estimated that customers of commercial health insurance in China will have paid $300 billion in written premiums. Additionally, China's emerging form of commercial health insurance, City Supplemental Insurance, could expand the number of insured patients in China, in turn allowing additional patients to access drugs that aren't on China's national reimbursement drug list. According to Du, 200 million to 300 million people could enroll by the end of 2025. 

Revolution Medicines 

Revolution Medicines is expecting initial data readouts in 2023 from several Phase I drug trials that it launched last year. 

For example, the Redwood City, California-based firm began trials for two of its RAS(ON) inhibitors, which directly target KRAS mutations, in 2022. The firm is studying RMC-6236 in a Phase I/Ib trial in patients with KRAS G12-mutant advanced solid tumors, including patients with KRAS G12A, G12D, G12R, G12S, or G12V-mutated cancers. Researchers began dosing patients with RMC-6236 in that trial in June, and an initial readout of safety and anti-tumor activity is slated for mid-2023, said Revolution CEO Mark Goldsmith. 

The other RAS(ON) inhibitor in clinic trials, RMC-6291, is undergoing a Phase I/Ib trial in patients with KRAS G12C-mutant advanced solid tumors. Goldsmith said he expects initial results from that study in late 2023 because RMC-6291 is in early development and there is a dearth of cancer patients with KRAS G12C-mutated tumors available for enrollment. 

Steve Kelsey, president of R&D at Revolution, added that the KRAS G12C-targeted treatment space is "extremely competitive," with Amgen's Lumakras (sotorasib) and Mirati Therapeutics' Krazati (adagrasib) already on the market and other KRAS inhibitors in development. That means many patients enrolling in Revolution's drug trials have already received a KRAS inhibitor, he said. 

On the other hand, "the uptake of KRAS G12C inhibitors outside the US is relatively low," Kelsey observed. "Opening sites outside the US usually allows access to a very large number of patients with KRAS G12C-mutant tumors that have not previously seen a KRAS inhibitor. Operationally, that's where we'll be going [for these trials]." 

Revolution expects to begin a Phase I trial for its KRAS G12D inhibitor, RMC-9805, in G12D-mutant solid tumors in mid-2023. The firm also unveiled a new candidate in its RAS(ON) pipeline, RMC-0708, which targets KRAS Q61H-mutant tumors. That drug is currently undergoing preclinical investigational new drug (IND) application-enabling studies. 

The firm is also expecting data on its RAS companion inhibitors, which are intended to be paired with RAS inhibitors and are designed to overcome treatment resistance. In the second half of the year, Revolution expects top-line data from a Phase II trial of its SHP2 inhibitor RMC-4630 combined with Lumakras in KRAS inhibitor-naïve patients with KRAS G12C mutations. Revolution also expects results from a Phase I trial of its mTORC1/4EBP1 inhibitor RMC-5552 in tumors with hyperactive mTOR signaling. 

"As of today, drug candidates in formal stages of development at Revolution Medicines inhibit the drivers of all major RAS-addicted forms of human lung, colorectal, and pancreatic cancer," Goldsmith said. "We are highly encouraged that the era of targeted treatment for patients with RAS cancers broadly is within reach." 

As of Sept. 30, 2022, Revolution had $655 million in cash, cash equivalents, and marketable securities, which Goldsmith said will fund planned operations through 2024. 

Ideaya Biosciences 

Ideaya Biosciences anticipates beginning a registration-directed Phase II/III melanoma trial for its lead candidate, the PKC inhibitor darovasertib, in Q1 this year. The South San Francisco, California-based drugmaker is planning to study darovasertib with Pfizer's ALK inhibitor Xalkori (crizotinib) in metastatic uveal melanoma and is preparing to discuss key design aspects of the trial with the US Food and Drug Administration, such as whether patients should be randomized to a comparator arm and involve a predictive biomarker. The company is expecting to conduct a randomized trial, said Ideaya CEO Yujiro Hata, and will propose enrolling metastatic uveal melanoma patients who have an HLA-A-negative serotype. 

"Our perspective is that we believe the highest probability of success and potentially fastest path to approval would be a focused trial in the HLA-A-negative setting," Hata said. The darovasertib-Xalkori combination has also shown activity in the HLA-A-positive setting, however, and according to Hata, Ideaya could seek approval in this population even if it pursues the HLA-A-negative serotype indication first. Ideaya hopes to discuss these biomarker-driven approaches with the FDA, too. 

Other agents in the company's pipeline include the PARG inhibitor IDE161, which Ideaya on Monday said it will study in a Phase I trial in homologous recombination repair-deficient cancers. In the first half of this year, the company also wants to move its preclinical-stage Pol Theta helicase inhibitor into first-in-human trials in homologous recombination repair-deficient cancers, including those harboring BRCA1/2 mutations. Ideaya has partnered with GlaxoSmithKline to evaluate the Pol Theta helicase inhibitor with GSK's PARP inhibitor Zejula (niraparib). Ideaya intends to further pick a drug targeting the Werner helicase to develop further with GSK in microsatellite instability-high cancers, specifically gastrointestinal tumors. 

Relay Therapeutics 

Relay Therapeutics is beginning to plan for commercialization of its lead candidate, the FGFR2 inhibitor RLY-4008, and hopes to kick-start clinical development of its breast cancer pipeline in 2023. 

In the first half of the year, Relay expects to report full dose escalation data from its Phase I/II study of RLY-4008 in unresectable or metastatic FGFR2-altered cholangiocarcinoma and other solid tumors. In the second half of the year, Relay expects the pivotal cohort of FGFR2-altered cholangiocarcinoma patients will be fully enrolled. While early data on RLY-4008 has been in cholangiocarcinoma patients, the firm is studying the drug's activity in other FGFR2-altered solid tumors and hopes to report results from the trial's expansion cohorts in the second half of 2023. 

"We're now starting to contemplate commercialization for the first of our assets," said Relay CEO Sanjiv Patel. "The commercial opportunity here has been on people's minds, and we commit to sharing the non-cholangiocarcinoma expansion cohort data to give you a sense of the size of the commercial opportunity that [RLY-4008] could have. With that, it's all about execution and getting this medicine to patients as rapidly as possible." 

Relay is also planning to report this year the first data from its roster of breast cancer candidates. Its PI3Kα inhibitor, RLY-2608, is being studied as a monotherapy and in combination with fulvestrant in a Phase I trial involving patients with PIK3CA-mutated advanced solid tumors, including breast, ovarian, cervical, and head and neck cancers. Initial data from that study is expected in the first half of the year. 

Later in 2023, Relay expects to begin clinical studies of RLY-5836, its second PI3Kα inhibitor. The firm will also nominate a drug candidate to advance clinically within its estrogen receptor-alpha degrader program in breast cancer this year. Meanwhile, its CDK2 inhibitor for breast cancer is expected to enter the clinic in early 2024, Patel said. 

"All of this leads to a very deep pipeline of breast cancer assets that we hope will transform the treatment of hormone receptor-positive, HER2-negative patients, and we look forward to sharing data for the first time this year," Patel said. 

Relay, based in Cambridge, Massachusetts, had $1.1 billion in cash, cash equivalents, and investments as of Sept. 30, 2022, which Patel said will fund the company's current operating plan into 2025.