Checkpoint targeting registration studies by end of 2018

James Oliviero, president and CEO

James Oliviero, president and CEO

Checkpoint Therapeutics (OTCQX:CKPT) is taking an “aggressive path forward” with its clinical programs and expects to be in registration studies at the end of 2018 with its lead targeted anti-cancer agent, CK-101, and lead immuno-oncology (IO) agent, CK-301.

“Because these compounds have validated targets, we believe we can quickly establish safe dosages, with sufficient efficacy signals, to potentially move from early-stage studies into Phase 3 development before the end of 2018,” James Oliviero, president and CEO, says in an interview with BioTuesdays.

“We are developing each of our drug candidates initially as monotherapies and once safety and efficacy is established, we then can move to combination studies with our compounds to achieve leading-edge immune-enhanced activity,” he adds.

Mr. Oliviero explains that by using combinations of two IO agents or an IO agent plus a targeted therapy, “we hope to achieve higher response rates plus durable response rates potentially lasting years by engaging the immune system, particularly killer T-cells, to attack and kill cancer cells. This is where cancer therapy is going.”

“By owning all component drugs in a combination therapy in-house, we also can achieve pricing leverage below a combination therapy created by two different companies,” he adds.

Checkpoint also is collaborating with TG Therapeutics (NASDAQ:TGTX) to develop IO antibodies in combination with TG’s targeted therapies for blood-based tumors, such as non-Hodgkin’s lymphoma and chronic lymphocytic leukemia.

“While we focus on solid tumors, TG will focus on hematological tumors and we’re eligible for milestones and royalties with their success,” Mr. Oliviero adds.

Checkpoint, which licensed its original technology in 2015 and went public in the fourth quarter last year, is a member of the Fortress Biotech (NASDAQ:FBIO) group of companies. Checkpoint hopes to up-list to NASDAQ this year.

checkpoint's strategy is to develop first-in-class or best-in-class combination treatments in targeted solid tumor cancers and liquid tumors in collaboration with tg therapeutics 

checkpoint's strategy is to develop first-in-class or best-in-class combination treatments in targeted solid tumor cancers and liquid tumors in collaboration with tg therapeutics 

The company’s portfolio now includes two IO monoclonal antibodies and four targeted anti-cancer agents. Three of the six compounds are considered lead programs: CK-301, CK-302 and CK-101.

In its IO portfolio, Checkpoint plans to file an IND in mid-2017 for its anti-PD-L1 antibody, CK-301, and begin a Phase 1 study in the third quarter. It also plans to file an IND in the first half of 2018 for its anti-GITR antibody, CK-302.

Both compounds, which were licensed from the Dana-Farber Cancer Institute, are being developed for the treatment of multiple forms of solid tumor cancers.

According to Mr. Oliviero, an anti-PD-L1 antibody removes the ability of cancer cells to shield themselves from attack by the immune system’s killer T-cells, while an anti-GITR antibody heightens the activity of T-cells to attack cancer cells.

“It’s like taking the brakes off the immune system and then hitting the gas pedal,” he adds. “With the portfolio we have, there’s also the potential to combine three agents for even greater synergy.”

Mr. Oliviero also points out that unlike most other anti-PD-L1 agents, “our IO compound retains native features for potentially greater killing power.”

Checkpoint’s lead targeted anti-cancer agent is an EGFR inhibitor, CK-101, which is currently in the dose escalation portion of a Phase 1/2 trial for the treatment of patients with non-small cell lung cancer. Enrollment in the Phase 2 portion of the study is expected to begin in the second half this year.

Mr. Oliviero explains that CK-101 is a third-generation EGFR inhibitor similar to AstraZeneca’s Tagrisso, which has been approved by the FDA for lung cancer patients with the T790M mutation. AstraZeneca predicts peak sales of Tagrisso of $3-billion, a substantial market opportunity that can support additional entrants.

In mice, CK-101 showed strong activity against T790M mutated NSCLC with increasing dose

In mice, CK-101 showed strong activity against T790M mutated NSCLC with increasing dose

“We think CK-101 could be the next best alternative to Tagrisso, given potential safety advantages, which we will have to ultimately support in the clinic,” he adds.

The Phase 2 portion of the CK-101 trial will enroll about 60 lung cancer patients with the T790M mutation confirmed by a diagnostic to exclude non-responders. The protocol is similar to the initial Tagrisso trial, with the same primary endpoint of overall response rate.

“If we see sufficient response activity in the first quarter next year, we’ll begin submitting plans for a registration trial with the FDA and non-U.S. regulatory authorities, and hopefully commence a registration trial by the end of 2018,” Mr. Oliviero says. “The plan is to develop CK-101 as both a monotherapy and in combination with our synergistic IO agents.”

Lung cancer with the T790M mutation has an estimated annual incidence of 40,000 patients in the U.S., EU and Japan.

The company also plans to begin a Phase 1b study in the next 12 months with its PARP inhibitor, CK-102. It also plans to file an IND in the second half this year for CK-103, its small molecule inhibitor of the BET protein, BRD4. The company is targeting another IND in 2018 for its anti-CAIX monoclonal antibody for the treatment of renal cell carcinoma and other solid tumors.

According to Mr. Oliviero, the goal of targeted anti-cancer therapy is to “smart bomb” specific cancer pathways or driver mutations. “Our four targeted anti-cancer agents each have unique mechanisms of action for targeting cancer cells, which adds diversification and the potential for many combinations with the IO side of the portfolio.”

Wangzhi Li, an analyst with Ladenburg Thalmann, in an initiation report last month, said Checkpoint’s pipeline resembles that of Beigene (NASDAQ:BGNE), which has a market cap of $1.5-billion, and Tesaro (NASDAQ:TSRO), which has a market cap of $8-billion, in many ways, but at an earlier stage.

“We believe Checkpoint is currently under-recognized and presents an attractive investment opportunity tapping into the combination therapy trend for cancer treatment,” he added.

Dr. Li started Checkpoint with a “buy” rating and $20 price target. On Thursday, the stock closed at $12.50, giving the company a market cap of $218-million.

checkpoint therapeutics' pipeline

checkpoint therapeutics' pipeline