NEW YORK - The 39th annual JP Morgan Healthcare Conference kicked off on Monday with several drug developers, specialty pharma companies, and molecular testing firms providing updates on their precision oncology products. Below are brief reports on the presentations covered by our team.
Merck KGaA CEO Stefan Oschmann is hoping the US Food and Drug Administration will approve its MET inhibitor tepotinib in the coming weeks. The FDA accepted Merck's new drug application for tepotinib last August as a treatment for metastatic non-small cell lung cancer with a MET exon 14 skipping mutation. This upcoming approval, among other promising products in the company's growing pipeline, strengthens Merck's confidence in being able to deliver €2 billion ($2.43 billion) in pipeline sales by 2022, Oschmann said.
In terms of pipeline updates, this year the Darmstadt, Germany-based drug developer is expecting a study of bitrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, to read out in second-line advanced or metastatic biliary cancer. Among the endpoints in the study, researchers are looking at objective response rates and durable responses based on patients' PD-L1 expression and microsatellite instability status.
The company is also developing bitrafusp alfa in first- and second-line HPV-positive cervical cancer and conducting a Phase I trial in triple-negative breast cancer. Danny Bar-Zohar, global head of development at Merck, noted that following the FDA's approval of atezolizumab (Genentech's Tecentriq) and pembrolizumab (Merck's Keytruda) in PD-L1-expressing TNBC, "we want more" options. The company has found in a small number of patients that bitrafusp alfa yields up to a 60 percent response rate in TNBC patients who overexpress HMGA2, and is futher studying this group.
The company is also focused on using real-world data to inform the safety and efficacy of its therapeutic products, a goal that has deepened amid the COVID-19 pandemic. Real-world evidence is a "vital part" of ensuring good clinical decision making and is a core strategic component of educating physicians about its products, said Rehan Verjee, president of EMD Serono, Merck's biopharmaceutical business. Such data will be particularly useful in driving adoption of tepotinib once it is approved and launched, he suggested, as it is a new drug in a new therapeutic class.
BridgeBio Pharma Co-founder and CEO Neil Kumar said that 2021 is likely to be the "most consequential year" for the company in terms of making progress toward its goal of becoming a leader in genetic medicines. Toward that end in the precision oncology space, the US Food and Drug Administration accepted a new drug application from BridgeBio and its subsidiary QED Therapeutics in December for infigratinib in FGFR-altered bile duct cancer. If approved this year, this could lead to a small amount of revenue for the company, according to Kumar, and demonstrate the ability of R&D and commercialization teams at BridgeBio to launch products on the market.
Kumar also highlighted two programs in the company's targeted oncology portfolio: a SHIP2 inhibitor that has entered the clinic and a RAS-targeted therapeutic program in the preclinical stage. In November, BridgeBio with its subsidiary Navire Pharma began enrolling and dosing patients in a Phase I study of its investigational SHP2 inhibitor, BBP-398, as a treatment for solid tumors harboring MAPK signaling pathway genetic mutations.
"We think SHP2 is going to be most interesting, not in the context of monotherapy, but rather in combination," Kumar said, adding that the company decided to advance the drug on its own, hoping to combine the drug with an EGFR inhibitor, such as osimertinib (AstraZeneca's Tagrisso), or Mirati Therapeutics and Novartis' investigational KRAS G12C inhibitor adagrasib.
In its RAS inhibitor program, Kumar predicted that the company will settle on a clinical candidate in the KRAS-mutant cancer setting later this year or early next year. The RAS franchise is "our biggest investment preclinically" involving around 40 scientists focused on modeling and structural work, he said.
Agios CEO Jackie Fouse said that the company's decision to sell its entire oncology portfolio to Servier Pharmaceuticals will help Agios become cash flow positive by 2025. The divestment, which Agios announced last month and expects to close by Q2 2021, is part of the company's plan to concentrate its pipeline on genetically defined diseases outside of cancer.
Under the terms of the sale, Agios will receive $1.8 billion upfront from Servier, of which it plans to return at least $1.2 billion to its shareholders through share buybacks. The company will also be eligible for $200 million in milestone payments for its IDH1/2 inhibitor vorasidenib should it be approved for IDH1/2-mutated brain cancer in the US prior to 2027.
Agios will continue to advance its oncology portfolio until the Servier deal closes later this year. The company projected net revenues for its blood cancer IDH-inhibitor ivosidenib (Tibsovo) in 2021 in the range of $160 million to $170 million. The company will file a supplemental new drug application for ivosidenib for IDH1-mutant cholangiocarcinoma in the first quarter of this year. Mature overall survival data for the drug in this indication will be presented later this month during the ASCO Gastrointestinal Cancers Symposium.
Ivosidenib is also being evaluated in combination with azacitidine for treatment-naïve IDH1-mutated acute myeloid leukemia patients, as well as for patients with relapsed or refractory IDH1-mutant myelodysplastic syndromes. The respective Phase III and Phase I clinical trials for these indications are expected to complete enrollment by the end of 2021.
Though Fouse was reluctant to speak definitively on behalf of Servier's plans for the oncology portfolio once the sale is complete, she expressed confidence that the company would continue to invest in AG-270, Agios' MAT2A inhibitor currently being developed for MTAP-deleted non-small cell lung cancer and pancreatic cancer.
Bristol Myers Squibb
Bristol Myers Squibb CEO Giovanni Caforio expects nivolumab (Opdivo) will return to growth after a seeing sales decline in 2020. In the third quarter, BMS reported nivolumab sales of $1.8 billion, a 2 percent decline from the same period last year. The company is slated to report Q4 revenues in February.
Caforio said nivolumab's recent launch as a first-line treatment for PD-L1-positive non-small cell lung cancer is "going very well." He cited several future opportunities for nivolumab in various metastatic cancer indications and as an adjuvant therapy. "We're building a really strong presence in the adjuvant space," he said.
He also cited positive data readouts last year from nivolumab trials in gastric, esophageal, and renal cancers as indicators that nivolumab will return to growth in 2021. BMS expects US and European approvals in 2021 for nivolumab in first-line HER2-negative gastric cancer, first-line esophageal cancer, and adjuvant muscle-invasive bladder cancer. Researchers are evaluating nivolumab outcomes by PD-L1 status in those indications.
At the same time, BMS is also preparing for the loss of exclusivity for nivolumab toward the end of the decade. The company's next oncology product launch is expected to be from its cell therapy franchise, featuring lisocabtagene maraleucel and idecabtagene vicleucel, which are currently being reviewed by the US Food and Drug Administration in diffuse large B-cell lymphoma and multiple myeloma.
Amgen's chairman and CEO Robert Bradway said that the company's KRAS inhibitor sotorasib, currently under US Food and Drug Administration review for KRAS G12C-mutated non-small cell lung cancer patients, represents what is likely one of the fastest ever registration-enabling programs in the industry. The agent, which moved from human studies to registration filing in roughly 28 months, is under regulatory review in both the US and EU, and the company plans to present Phase II NSCLC data at the upcoming International Association for the Study of Lung Cancer conference on Jan. 29. Amgen is also enrolling KRAS G12C-mutated NSCLC patients to a Phase III clinical trial comparing sotorasib against docetaxel.
In addition, the company is evaluating more than 10 combination regimens involving sotorasib, and initial data from these studies will be presented in the first half of 2021. Data from a Phase II trial of sotorasib in KRAS G12C-mutated colorectal cancer will also be presented in the first half of this year.
Mirati Therapeutics CEO Charles Baum discussed the progress on the KRAS G12C inhibitor adagrasib. The company is evaluating adagrasib as both a monotherapy and in combination with other checkpoint inhibitors in non-small cell lung cancer and colorectal cancer.
The Phase II trial evaluating adagrasib in second-line NSCLC is expected to report results this year, and Mirati plans to file a new drug application in this indication with the US Food and Drug Administration in the second half of 2021, Baum said. Early results from the trial showed a 45 percent objective response rate for patients taking adagrasib alone. This study, along with an earlier Phase I trial, found that patients with both KRAS G12C and STK11 mutations fared particularly well on the drug, spurring Mirati to initiate a Phase I trial specifically enrolling patients with both mutations.
Mirati has several combination studies in NSCLC, exploring adagrasib with already approved drugs, such as pembrolizumab (Merck's Keytruda), afatinib (Boehringer Ingelheim's Gilotrif), and palbociclib (Pfizer's Ibrance). The company is also evaluating adagrasib with cetuximab (Eli Lilly's Erbitux) in second-line colorectal cancer, and pairing its drug with Novartis's SHP2 inhibitor and Boehringer Ingelheim's SOS1 inhibitor.
"We started pretty aggressively and early in combinations," Baum said. "We're trying to be as aggressive as possible to move into earlier lines of therapy. We wanted to move into first-line treatment as soon as we could. That is the overriding intention of the combination trials."
Mirati is also planning to file an investigational new drug application for its KRAS G12D inhibitor MRTX1133 this year as the drug moves into clinical studies. Finally, the company has ongoing Phase II and Phase III trials of sitravatinib, which targets RTK receptors, in combination with nivolumab (Bristol Myers Squib's Opdivo) in NSCLC.
Takeda President and CEO Christophe Weber said that the company is targeting $47 billion in revenues by 2030 with a host of new products expected to launch across four key disease areas, including oncology, in the coming years. The oncology pipeline features the company's EGFR/HER2 exon 20 inhibitor mobocertinib, which has breakthrough therapy designation from the US Food and Drug Administration for the second-line treatment of non-small cell lung cancers harboring EGFR exon 20 insertion mutations.
Takeda is hoping to garner accelerated approval in the US for this agent during fiscal year 2021 based on data from a Phase II trial. Down the line — potentially in fiscal year 2023 — the company hopes to advance the agent to the first-line setting for this same NSCLC subpopulation. This will be contingent on the readout from the agent's Phase III trial in FY22.
Chicago-based diagnostics company Tempus provided the first look at Tempus One, a portable, voice-enabled, artificial intelligence-powered device that oncologists can query for information about their patients' molecular test results, clinical trial options, and treatment outcomes. According to Tempus Founder and CEO Eric Lefkofsky, the cube-shaped device that can rest on a desk or fit into a doctor's pocket is the result of several years of R&D at the company and is now available to select oncologists through a beta launch.
Lefkofsky said the device represents the "physical manifestation" of Tempus' database, which contains not only patients' molecular test results, but also information from other pathology and imaging tests, treatment outcomes, as well as structured and unstructured data stored in their electronic health records. The device queries nearly 30 petabytes of data in Tempus' database, which is growing at 1 petabyte per month.
"We're fundamentally trying to make diagnostics as intelligent as we can by combining vast amounts of real-time data," Lefkofsky said, adding that Tempus decided to use AI to improve doctors' access to lab test results, since that's an aspect of their patients' care that they interact with daily. "AI will enter healthcare through intelligent diagnostics as the first major step," he predicted, "and eventually work its way into AI-enabled therapeutics or AI-enabled clinical support."
There are approximately 7,500 oncologists contributing their patients' information to Tempus' platform and around 2,000 Tempus employees are working on this AI-enabled diagnostic solution, collecting, organizing, and contextualizing the real-world data. Tempus is also collaborating with several healthcare organizations, through which it gleans structured and unstructured patient information from data warehouses or directly from the EHR. "We're pinging that database periodically to get updates," Lefkofsky said, explaining that every six to 12 months Tempus restructures the clinical data on a patient in its database using technology and human curators.
Lefkofsky said that oncologists can ask Tempus One the types of questions they might ask a tumor board. For example, oncologists may ask the cube what actionable molecular markers a patient has, a patient's prognosis based on their cancer diagnosis and molecular markers, the disease-associated germline mutations the patient may have inherited, and the clinical trial closest to the ordering physician.
During the beta launch, Tempus wants oncologists to test Tempus One in their clinical workflows. The company plans to broadly launch the device later this year. Eventually, Lefkofsky envisions that the device will be able to query, diagnose, and guide care decisions for patients longitudinally at every phase of their journey through the healthcare system.
Guardant Health CEO Helmy Eltoukhy said that his firm, formerly focused solely on blood-based cancer genotyping, plans to launch two new products this year, including a comprehensive tissue sequencing assay that would compete with tests from leaders in the space like Foundation Medicine, Caris Life Sciences, and others.
The company also intends to release a minimal residual disease test it has now dubbed GuardantReveal, formerly known as Lunar-1, by the end of the first quarter of 2021, although the long-term trials assessing the assays clinical impact are still ongoing.
Guardant said the Reveal assay has a seven-day turnaround time and is intended to detect residual disease and surveil for emerging recurrences in patients with earlier-stage cancer who have had surgery or other treatments with curative intent.
Currently the test is for use only in colorectal cancer patients, but the company is also working to validate it in additional tumor types. Unlike some other blood-based MRD tests, such as Natera's Signatera, which require upfront tissue sequencing to create patient specific liquid biopsy assays, GuardantReveal is universal and performed directly on blood without the need for tissue samples.
The firm's most recent data for the assay demonstrated 91 percent sensitivity and 100 percent specificity for recurrence detection.
Outside of these new product launches, the Redwood City, California-based firm also believes it will see growing adoption of its existing tumor genotyping tests, following the approval it received last year from the US Food and Drug Administration for the CDx version of its core assay, Guardant360.
The company believes that Guardant360 CDx — which is approved for genomic profiling of all solid tumors, and as a companion diagnostic to determine patient eligibility for the EGFR-targeting drug osimertinib (AstraZeneca's Tagrisso) — will be critical in accelerating adoption of liquid biopsy testing, especially among oncologists who have been on the sidelines with respect to comprehensive genomic profiling.
Guardant also launched an update to the LDT version of Guardant360 last year, adding both additional targets and what the firm believes to be a best-in-class blood-based calculation of tumor mutational burden.
Eltoukhy said that Guardant's 2020 Q1, Q2, and Q3 test volumes increased 60 percent, 15, percent, and 28 percent respectively year over year, growing to just under 17,000 tests in the third quarter last year, driven by further shifts in the cancer genotyping market to a blood-first paradigm, and expansion in the use of repeat testing.
But as much progress as the firm has made, it's CEO said that it's clear that Guardant is still very much in the early innings of adoption for the 700,000 patients that have metastatic disease of solid tumors, and there is "ample room" for it to further fill the lingering gap between clinical guidelines and clinical practice.
Areas outside of standard tumor profiling that the company continues to pursue for Guardant360 include the molecular assessment and tracking of therapy response.
Finally, Eltoukhy reiterated Guardant's confidence that it is on track to complete enrollment of the ongoing prospective study of its Lunar-2 colorectal cancer screening assay by the end of this year. If successful, this ECLIPSE trial is expected to play a pivotal role in a potential FDA submission.
Myriad Genetics CEO Paul Diaz further discussed the company's strategy to reorganize its business after several quarters of declining revenues and negative impact from the COVID-19 pandemic. After a review of its business, the company recently announced that it would focus on growing its leadership position in the women's health, hereditary cancer, and mental health segments, and concentrate on growing its presence in certain international markets, such as Germany, France, and Japan. Meanwhile, the company will sell its autoimmune business, including the Vectra DA rheumatoid arthritis test, the Myriad RBM pharmaceutical contract research services business, and the myPath Melanoma dermatology test.
As part of its international growth strategy, the company announced on Monday that it was collaborating with Illumina to create a kit-based version of its myChoice CDx for international markets. The partnership will leverage Illumina's customer base for its TruSight Oncology 500 NGS test, and Myriad's experience advancing its homologous recombination repair deficiency lab-developed test, which gauges BRCA1/2 mutations and a genomic instability score based on analysis of three DNA damage biomarkers.
Diaz said this will hopefully be one of many partnerships that will grow Myriad's international presence. Historically Myriad has taken a "go it alone" approach, he acknowledged, but as part of its reorganization, the firm will look for partnership opportunities with other companies, health systems, employers, and payors.
He highlighted the GeneSight PGx test, which helps doctors guide treatments for patients with depression and other psychiatric conditions, as another growth opportunity, particularly during the COVID-19 pandemic when people are struggling with mental health issues. The company began shipping at-home sample collection kits for the test over the summer and has noted growing interest among payors for strategies to address the mental health crisis.
Meanwhile, due to the pandemic, the company is remaining conservative and holding off on providing future revenue guidance. "Given the resurgence of COVID, and [the fact that] the last couple of days have been just horrific, one should be prepared … for a pretty flat couple of quarters," Diaz said. Even though the company has implemented new sales strategies to mitigate the impact of the pandemic, he acknowledged that "even hanging on to the gains we have made requires a lot of work."
NeoGenomics CEO and Chairman Douglas VanOort said that the firm expects to grow at twice the market rate due to significant company-specific growth drivers that will affect its clinical, pharma, and nascent informatics divisions.
Fort Myers, Florida-based NeoGenomics sees itself as a one-stop shop for providers in the cancer community, working with more than 4,400 institutions, hospitals, and oncology practices to ensure that cancer patients can benefit from high-quality diagnostic assays.
Highlighting the growth of its informatics division, which was launched last year, VanOort noted that it uses data generated from about 1 million of the firm's annual clinical division assays.
NeoGenomics is rapidly scaling the informatics business and experimenting with a number of product offerings and services for pharma partners, including matching patients with therapies and clinical trials. The firm hopes to eventually generate $100 million in annual revenue from its informatics business.
"Because companion diagnostics and the ability for us to leverage our vast [oncology] database is so important to us, we created the informatics business," VanOort said. "We're basically leveraging … [the] database to help meet the needs of pharma companies, providers, payors, and in the future, even patients."
VanOort estimated that nearly one-third of NeoGenomics' expected 2021 revenues could stem from its NGS offerings, as well as its pharma and informatics divisions.
After adding a research lab in China late last year, NeoGenomics now plans to launch a new lab in Fort Myers by the second half of 2021. The firm expects to use the lab to invest heavily in its next-generation sequencing (NGS) capabilities, with plans to eventually become a market leader in NGS.
NeoGenomics noted its pharma business is growing about twice as fast as its clinical business. The firm has placed about $180 million worth of signed pharma contracts in backlog in the last two quarts, while certain short-term contracts have converted to longer projects.
Despite the resurgence of COVID-19 cases in Q4 2020, NeoGenomics noted that it has not impact test volumes as much as it did earlier in 2020. The firm has noticed that a lot of providers have remained opened and have procedures in place for seeing patients. However, NeoGenomics acknowledged that its clinical trials have dealt with delays due to limited testing volumes at some of its sites.
VanOort also highlighted NeoGenomics' work with Cambridge, UK-based Inivata, noting that the team commercially launched its InVision-First Lung NGS assay last fall. NeoGenomics acquired a minority stake in Inivata, and said it has seen promising validation data on Inivata's RaDaR technology for monitoring residual disease.
In conjunction with its presentation, Adaptive Biotechnologies announced a new partnership with AstraZeneca focused on applying Adaptive's ImmunoSeq T-Map product across the pharma giant's oncology portfolio.
The deal marks the "first extension of [ImmunoSeq] T-Map into cancer," Adaptive CEO and Cofounder Chad Robins said in a conference session. The product quantitatively maps T-cell receptors to antigens that elicit an immune response. "It's the first pure data play in cancer" stemming from the firm's antigen mapping partnership with Microsoft, Robins said, adding that the mapping data "can inform signatures of immune response to AstraZeneca's cancer therapies."
Throughout 2020, the firm also signed 25 core lab partnerships around ImmunoSeq, the firm's research assay, he noted, and the AstraZeneca deal helps kick off a year that Robins suggested would be filled with important "catalysts" for the company.
In clinical testing, the firm is expanding the number of indications for its ClonoSeq assay and will soon offer blood-based testing. In acute lymphoblastic leukemia, such testing is "right around the corner," Robins said, and multiple myeloma trials are ongoing. Blood-based testing should double the size of the potential patient pool for ClonoSeq, he added.
The firm also launched direct-to-patient marketing campaign for ClonoSeq.
Adaptive President Julie Rubinstein also said the firm was seeing interest in its T-Detect COVID test, which uses TCR profiles to determine whether an individual was infected by SARS-CoV-2. "There's definitely consumer interest in knowing if they had COVID," she said.
The firm's therapeutics projects are also progressing. The firm has opened a new lab in South San Francisco, California to contribute to its personalized cancer therapy collaboration with Roche subsididary Genentech, which is expected to file an investigative new drug application for their first shared product in Q1 2021. The partners expect to have a second investigative new drug filing ready to submit to the US Food and Drug Administration in 2022, Adaptive CSO Harlan Robins said.