NEW YORK – On the last day of the 41st Annual JP Morgan Healthcare Conference, companies discussed how economic pressures and new licensing deals have impacted their precision oncology drug development priorities, while others provided updates on their pipelines.
Below are brief reports on individual presentations from the conference on Thursday. Summaries from Day 1, Day 2, and Day 3 are available here, here, and here.
Elevation Oncology
Elevation Oncology last week went through some major changes. The New York-based company announced it was reducing its workforce by 30 percent, pausing development of the anti-HER3 IgG2 monoclonal antibody seribantumab as part of a pipeline reorganization, and that Shawn Leland was resigning as CEO. This week, interim CEO Joseph Ferra discussed these changes at the conference.
In June, Elevation reported initial efficacy data on seribantumab from the Phase II CRESTONE trial involving 12 patients with NRG1 fusion-positive advanced pancreatic and non-small cell lung cancer. Thirty-three percent of the patients responded to seribantumab, and the disease control rate was 92 percent. But as of last week, Elevation has paused enrollment in CRESTONE and said it will put its resources toward developing the Claudin18.2-targeted antibody-drug conjugate EO-3021 and only resume development of seribantumab in collaboration with a partner.
With the focus now largely on EO-3021, Ferra said at the conference that Elevation's Shijiazhuang, China-based partner CSPC Pharmaceutical is already recruiting patients into a Phase I trial of EO-3021 in China, and a US trial is slated to begin in the second half of 2023. The company plans to present preclinical proof-of-concept data on EO-3021 at a medical meeting in the first half of 2023.
EO-3021 targets Claudin18.2, which is overexpressed in a range of solid tumors. Ferra said patients with Claudin18.2-expressing tumors currently have limited treatment options as expression of this target does not overlap with HER2 or PD-L1 expression, based on which patients can receive HER2 targeted therapy or immunotherapy, respectively.
In addition, Elevation plans to invest in discovering other selective cancer therapies, including investigating genomic drivers of cancer in partnership with Caris Life Sciences.
Elevation had $90.3 million in cash at the end of 2022, which provides a cash runway into the fourth quarter of 2024, according to Ferra.
Zymeworks
Zymeworks is focusing on its early-stage drug pipeline in 2023 after out-licensing its lead candidate zanidatamab to Jazz Pharmaceuticals at the end of last year.
The deal with Jazz is worth up to $1.76 billion, and Zymeworks already received $375 million in upfront and option payments for the rights to zanidatamab. With the deal, Jazz gained rights to the drug in the US, Europe, Japan, and other territories and is taking over all R&D costs for the drug. This allows Zymeworks to reallocate funding to its early-stage pipeline programs, CEO Kenneth Galbraith said.
Vancouver-based Zymeworks had a cash balance of $490 million at the end of 2022, which provides cash runway through 2026, Galbraith noted. The company is also expecting to receive milestone payments from Jazz and its other zanidatamab licensing partner BeiGene, which holds rights to the drug in the Asia-Pacific region, excluding Japan and India.
"We put ourselves in a position where we are financially strong enough to take advantage of all the opportunities that come out of our R&D engine," Galbraith said. "It's very important to find a way to finance the good opportunities that come out of it and not have to shelve them or delay them."
Zymeworks will continue managing the ongoing trials of zanidatamab, which is being studied in HER2-positive gastric, biliary tract, and breast cancers.
Its other clinical candidate, zanidatamab zovodotin, a drug that combines zanidatamab with a proprietary cytotoxin that delivers cell-killing payloads to tumor cells, is currently being studied in a Phase I trial in advanced or metastatic HER2-expressing cancers. Zymeworks is retaining rights to zanidatamab zovodotin.
This year, the firm expects to report data from the Phase I study of zanidatamab zovodotin, and enroll additional cohorts of non-small cell lung, gastroesophageal, ovarian, colorectal, and breast cancer patients.
Zymeworks is also focused on completing investigational new drug (IND) application-enabling studies for two preclinical programs: ZW171, a bispecific mesothelin and CD3 T-cell targeted drug, and ZW191, a folate receptor-alpha and TOP1 targeted drug. ZW171 could be a potential treatment for pancreatic cancer, ovarian cancer, and mesothelioma, and ZW191 could have activity in ovarian and other gynecological cancers. Galbraith said the company hopes to submit INDs for both candidates in 2024.
"We have a number of technology platforms [for drug development] that we've applied specifically for our partners' products through our history," Galbraith said. "Our intention going forward is to apply these [platforms] for our own portfolio more so than for other partners. We're going to try and use these platforms to develop five new INDs in five years."
Achilles Therapeutics
In 2023, Achilles Therapeutics is expecting to dose 15 to 20 additional non-small cell lung cancer and melanoma patients in its ongoing CHIRON and THETIS trials evaluating its clonal neoantigen-reactive T-cell (cNeT) therapy. The Phase I/II CHIRON trial is assessing the safety, tolerability, and preliminary efficacy of the cNeT therapy, ATL001, in advanced, previously treated NSCLC patients; and the Phase I/II THETIS trial is gauging the safety, tolerability, and preliminary efficacy of the same therapy, either alone or in combination with Bristol Myers Squibb's checkpoint inhibitor Opdivo (nivolumab) in advanced, previously treated melanoma patients.
London-headquartered Achilles expects to see additional confirmed responses from patients in these trials, and to home in on biomarkers of clinical activity. "We're going to use our translational science platform to identify [cancer] features, … to deconvolute the [therapy's] mechanism, and to continue to push the process forward," said Achilles CEO Iraj Ali, adding that the goal is to lock in a pivotal study of the novel therapy.
Toward that end, Achilles has scaled up production capacity at the Royal Free Hospital, its good manufacturing practices facilities in England and the Cell & Gene Therapy Catapult manufacturing center, which the firm opened in 2022. Additionally, Achilles is working with a contract development manufacturing organization, the Center for Breakthrough Medicines, near Philadelphia. Ali said these facilities should be sufficient to deliver on the firm's clinical goals through Phase III trials.
Achilles' personalized immunotherapies involve targeting clonal neoantigens unique to individual patients' cancer cells using autologous T cells. The firm uses its genomic analysis platform, Peleus, to identify the tumor targets, and patient-derived dendritic cells to "educate" the T cells to target the clonal neoantigens. The firm shared encouraging, albeit early, safety and anti-tumor activity data from the two ongoing trials toward the end of 2022 and plans to present additional data in 2023.
Ali also shared specifics on how the firm is approaching product characterization and potency assays — a process that other companies developing novel cell therapy approaches have struggled with in recent years. While certain aspects of these assays are proprietary, Ali said Achilles is using "very detailed flow cytometric analysis" to look at cytokine secretions such as interferon gamma and tumor necrosis factor alpha. With regard to biomarker identification, "what we want to do is identify the canonical features that predict for whether the patient will respond," Ali added. "That's how we intend to move the efficacy envelope forward on our product."