BIO Notebook, Day 4: Annual Convention Winds Down With Oncology In The Spotlight

Scrip closed out BIO International Convention on June 22 in San Diego with an oncology-packed day, including a panel discussion of next-generation cancer drugs and interviews about novel discovery and development platforms.

The panel discussion titled "Shooting For The Moon: Creating The Next Generation Of Cancer Killers" was moderated by this Notebook's author and the speakers included PsiOxus Therapeutics Ltd. CEO John Beadle, Bicycle Therapeutics Ltd. Chief Scientific Officer Nicholas Keen, Unum Therapeutics Inc. President and CEO Charles Wilson and Immune Design Corp. Chief Scientific Officer Jan ter Meulen.

Two points were especially striking during the hour-long discussion. All of the panelists agreed that regulatory hurdles are not an issue for novel oncology drugs, including therapeutics with truly novel modalities, such as PsiOxus's oncolytic viruses or Bicycle's proprietary peptides that incorporate characteristics of several other modalities, including small molecules and monoclonal antibodies. (Also see "Finance Watch: Bicycle Spins Toward Clinic With $52m Round; Stock Spikes Spur Offerings" - Scrip, 1 Jun, 2017.) The US FDA, European Medicines Agency (EMA) and other regulators generally are supportive and have not made it more difficult for these treatments to navigate the regulatory process.

One of the biggest challenge for the field actually is the availability of preclinical models that accurately predict the success of immuno-oncology and other cancer drugs. More biomarkers also are needed to tell whether an immuno-oncology agent will work in one patient or another. Truly predictive preclinical models are essential to using capital more efficiently in this field; they would allow drug developers to test their therapies for the right indications and populations before starting clinical trials, which would allow rapid decision-making on how to move on to a different study when one trial fails.

Scrip also spoke with Atreca Inc. and Vaximm AG on June 22 and had a conversation with a Merck & Co. Inc. business development executive on June 21 about deals related to the immuno-oncology blockbuster Keytruda (pembrolizumab) and other parts of the big pharma's portfolio.

Atreca Scours Survivors' Samples For Treatment Clues

Atreca has not disclosed the specifics for any of its three immuno-oncology drug discovery programs, but the novel antibodies' targets were identified with the company's intriguing Immune Response Capture (IRC) technology platform.

Redwood City, Calif.-based Atreca has used its IRC platform to investigate the responses of about 150 cancer patients who appear to have been cured by immunotherapies, hunting for antibodies that present themselves as those super responders with long, durable remissions were treated with immuno-oncology drugs, such as PD-1/PD-L1 inhibitors. The company then screens some of those antibodies to test their response in the presence of cancer cells; those that attack cancer cells may then be developed as therapeutic antibodies.

Atreca closed a $56m Series A round in 2015. (Also see "FINANCE ROUNDUP: A New VC Fund, A $60m Collaboration Boost, And 14 Funding Rounds" - Scrip, 18 Nov, 2015.) The company also signed a deal with Johnson & Johnson in 2014 to put its IRC platform to work in autoimmune diseases. (Also see "BioNotebook: Four deal updates, a venture funding round and a milestone fee" - Scrip, 5 Dec, 2014.)

"This is all patient-based," Atreca Senior Vice President and Chief Scientific Officer Norman Michael Greenberg told Scrip. "We are not starting with animals or disease models." The company gets its tumor samples from a variety of academic, biopharmaceutical and other partners.

Atreca has found antibodies that are expressed across multiple tumor types in immunotherapy-treated cancer survivors. Greenberg said the antibodies could be used in combination with checkpoint inhibitors to improve response to those drugs in indications where the immuno-oncology drugs are known to work and to help non-responders in other tumor types go into remission – otherwise known as turning cold tumors hot.

He noted that Atreca will publish a paper soon to shed a little more light on its technology, which could help the company find new partners. Those could include companies that are trying to better understand patients who already respond to their therapies as well as drug developers in need of novel antibodies for antibody-drug conjugates or T cell receptor sequences for T cell therapies.

Vaximm Finds First Combo Partner; Trial Starting Next Year

Scrip last spoke with Vaximm CEO Matthias Schroff at the BIO-Europe conference in November when the company was looking for partners to test its oral T cell immunotherapies in combination with checkpoint inhibitors. (Also see "Vaximm Seeks Pharma Partners For T-Cell/Checkpoint Inhibitor Combos" - Scrip, 29 Dec, 2016.) The company's first clinical candidate VXM01 targets VEGFR-2 to activate T cells so that they attack the tumor vasculature; it also attacks cancer cells directly in several tumor types.

Basel, Switzerland-based Vaximm's partnering strategy in 2016 delivered a partnership in 2017: In May the company said it signed an agreement with Merck KGAA and Pfizer Inc. to test VXM01 in combination with the companies' PD-L1 inhibitor Bavencio (avelumab). Vaximm will be responsible for conducting two open-label Phase I/II clinical trials in glioblastoma and metastatic colorectal cancer.

The company reported single-agent clinical trial results for VXM01 in glioblastoma during the American Society of Clinical Oncology (ASCO) earlier this month. Seven of the eight patients treated with the therapeutic vaccine in the Phase I trial went on to surgery and tumor samples extracted during those procedures showed that one patient had an objective and durable response, while three others achieved stable disease.

The results were so encouraging in this patient population with generally poor prognoses that Vaximm decided to enroll another eight patients, Schroff told Scrip at BIO International, noting that enrollment has reached 14 patients.

The forthcoming combination studies with Bavencio will test the company's hypothesis that PD-1/L1 inhibitors could keep the T cells activated by VXM01 active for longer periods. The first of those studies will begin in early 2018 with data expected in 2019, but biomarker results from the small Phase I single-agent study reported at ASCO hinted that Vaximm's theory is correct.

"Patients with PD-L1 expression that decreased did better and those with rising PD-L1 did worse," Schroff said. "There's a clear synergistic effect."

Merck's Dealmaking Strategy Shift Opened New Doors

A lot of Merck & Co's deals these days center around its PD-1 inhibitor Keytruda and the company's immuno-oncology priorities. Deals are as simple as clinical trial collaborations in which no money is on the table other than Merck agreeing to supply Keytruda for the partner to use in combination with its own immunotherapy, but run the gamut of licensing transactions to acquisitions.

Those deals and transactions related to Merck's other therapeutic areas, including neuroscience, cardiovascular disease and diabetes, benefit from a more open-minded business development strategy, Senior Vice President of Business Development and Licensing Ben Thorner said in a June 21 interview.

"If you roll the clock back a few years, Merck used to be known for a methodical approach to business development. We had a list on our website of targets that we were interested in and that was a well-intentioned effort to recognize gaps in our own clinical portfolio," Thorner said. "But as we stepped back and took a look at that, we realized that academic and other researchers are doing science their way and are doing things that are interesting or hard or that we haven't thought of."

He continued: "If we are looking for extraordinary molecules, like Keytruda, that will have extraordinary impact on medical progress, those are likely to come from outside of Merck. Now as we go out to look for assets to license or acquire, we are open-minded. Beyond our therapeutic areas and within those areas, there are opportunities that are new and novel and completely different from what we are looking at inside" of Merck.

That approach has resulted in transactions like last year's acquisition of Afferent Pharmaceuticals Inc. for $500m up front and up to $750m in regulatory and commercial milestone fees. (Also see "Merck To Get Chronic Cough P2X3 Inhibitor Candidate With Afferent Buy" - Scrip, 10 Jun, 2016.) Afferent was developing a P2X3 antagonist for chronic cough, which generated some initial skepticism about the company within Merck, since the indication was not something in its portfolio at the time, but research into the condition eventually showed that it was an opportunity worth pursuing, Thorner said.

"We are very open to dealmaking, whether it be M&A or licensing or any other types of transactions. We look at science that's interesting to us, but we also talk with the company [we're negotiating with] about what works with them," he noted. "Afferent and [the early 2016 acquisition of IOmet Pharma Ltd.] ended up as M&A, really because those companies had pretty focused portfolios. It wasn't clear that there was a lot for those companies to be doing beyond their existing portfolio."

But in a recent deal with Teijin Ltd. Merck and its partner opted for a licensing deal, because "we're partnered on a particular asset, but the company retained the rest of their portfolio," Thorner said.