Michael McCullar
OnQuality Pharmaceuticals CEO Michael McCullar, PhD, MBA

Immunotherapies, targeted therapies and cell therapies have reshaped the treatment landscape for cancer over the past decade, and are expected to more than double the global oncology drug market in four years, to $540.6 billion in 2026 from $223.21 billion this year, according to The Business Research Co.

Yet the new cancer therapies are also associated with side effects resulting from their damage to non-cancer cells, as a receptor or pathway targeted for inhibition also plays a role in normal cells, such as with vascular endothelial growth factor (VEGF) receptor or epidermal growth factor (EGF) receptor inhibitors. Many patients respond to those side effects by reducing their therapy dosage or completely discontinuing treatment—30% and 17%, respectively, according to one study.

Developing therapies that treat cancer therapy-related side effects at their molecular source is the focus of OnQuality Pharmaceuticals, a Shanghai-based drug developer with a U.S. headquarters in Seattle. OnQuality recently announced positive news for its lead candidate OQL011, an ointment designed to treat Hand-Foot Skin Reaction (HFSR) by locally activating VEGF downstream signaling pathways.

OnQuality reported positive topline data from part 1 of its Phase II NOVA-II trial (NCT04088318) showing that OQL011 met the study’s primary endpoint by meeting the company’s expectations of safety, efficacy and reduced patient-reported HFSR-related pain—down to grade 0 or 1 as per NCI CTCAE v5.0 grading of palmar-plantar erythrodysesthesia (PPE).

HFSR is characterized by redness, swelling, discomfort or pain, and blistering in the palms of the hands or the soles of the feet. HFSR is a common side effect of tyrosine kinase inhibitors, including VEGF receptor (VEGFR) inhibitors used for treating cancer.

VEGFR inhibitors impair vascular repair mechanisms that play a key role in areas of the body exposed to high pressure and repetitive force, such as the palms and soles.

OnQuality CEO Michael McCullar, PhD, said the company plans to advance OQL011 to part 2 of NOVA-II during the first quarter. In part 2, OQL011 will be administered at a higher dose level compared with three doses studied in part 1.

NOVA-II is a multicenter, randomized, double-blinded, vehicle-controlled, dose-ranging trial designed to assess the safety and efficacy of OQL011 compared to vehicle ointment in treating VEGFR inhibitor-associated HFSR. To be eligible for NOVA-II, patients must be receiving VEGFR inhibitor-based anticancer monotherapy or combination therapy and show a PPE grade of 2 or higher for HFSR severity.

“There are lots of new therapies developed for cancer in, especially in the past 10-15 years. However, the side effects are an untapped area, so we do feel there is a gap there on which we need to focus, and somebody is going to need to focus,” Hong Tang, MD, Chief Medical Officer and co-founder of OnQuality, told GEN Edge. “We thought it’s a good, good position for us to focus in the huge unmet need of cancer supportive care.”

Challenging market

One potential reason why it remains a huge unmet need: The global cancer supportive care drug market is set to grow much more slowly than the overall cancer drug market over the next decade, to $24.4 billion by 2030 from $19.63 billion in 2020. At a compound annual growth rate of 2.2%, that would put the size of the market last year at $20.06 billion.

Reflecting the challenge of that market: Lugano, Switzerland-based Helsinn announced in January that it will evolve from specializing in cancer supportive care to a “Fully Integrated Targeted Therapy” focus that will expand the company’s focus to targeted cancer drugs. Among them: A fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor for previously-treated locally advanced or metastatic cholangiocarcinoma (CCA) harboring an FGFR2 fusion or rearrangement, and a RET tyrosine kinase inhibitor currently in a Phase I/II trial.

Helsinn said it intended to reinvest about 35% of revenues from existing commercial engine of cancer therapeutic and supportive care products into targeted therapeutics R&D over the next five years.

The National Cancer Institute lists 63 “drugs approved for cancer-related conditions,” led by nausea and vomiting (seven drugs), followed by three conditions with six approved drugs each: Anemia, drug toxicity (severe side effects) and thrombocytopenia.

In contrast, nearly 400 drugs have been approved for cancer indications by the FDA since 2009, based on 332 tallied between 2009–2020 in a study published in JAMA and another 59 approvals listed by the FDA between January 1, 2021 and January 26 of this year.

Should it win approval, OQL011 would join about a dozen drugs indicated as VGRF receptor inhibitors. OQL011, developed internally, was found in cell and animal studies to restore the VEGFR rsignaling pathway.

“This way, we could address the hand-foot skin reaction, which is the most common side effect, causing pain, blisters, and rashes. And because it’s on the hands and feet, they impact our patients’ quality of life, including taking care of themselves—it’s just severe,” Hong said.

The duration of NOVA-II will depend, Hong said, on the global COVID-19 pandemic. Part 1 of the trial was delayed by COVID-19-related shutdowns, she acknowledged.

“If the COVID-19 situation is better, the enrollment could be quite quick, and maybe six months to a year. It depends on, again, this COVID situation,” Hong said.

In NOVA-II, Hong added, “We’re trying to see whether we could risk—heal the skin reaction and address the toxicity, but it also looks at the broad exposure of our drug, as well as the pain alleviation in quality of life.”

OQL011 is OnQuality’s only clinical-phase candidate. The company’s pipeline also includes four preclinical candidates. Two are in IND-enabling phases: OQL023 for EGFR inhibitor-induced skin rash and OQL033 for chemotherapy-induced hand-foot syndrome.

“EGFR inhibitor-induced skin rashes are most often seen on the face, so people feel very bothered because people just don’t want to have rash on their face. And it could have other symptoms like irritation—itchiness that sometimes cause infection,” Hong said.

She said EGFR inhibitor-induced rash has been named the top concern by cancer patients who are receiving EGFR inhibitor treatment, usually patients being treated for lung and colon cancer.

Clinic-bound candidates

OnQuality’s other two pipeline candidates are in discovery phases: OQL041 for EGFR inhibitor-induced diarrhea and OQL051 for chemotherapy-induced diarrhea.

“We’re advancing ‘051 quite quickly so on that one, we hope we’re getting to clinical stage in the next year, and ‘041 maybe after then,” Hong said.

She added that the pace of preclinical studies has also been slowed down by COVID-19.

Across the pipeline, McCullar said: “Next year at this time, we could have OQL011 in a Phase III study but also have meaningful clinical trials with ‘033 and ‘023, as well as pushing forward with a Phase I for OQL051 in chemotherapy-induced diarrhea.”

Privately-held OnQuality has raised a total $40 million. Most of that consists of an initial $15 million Series A round that grew into a “Series A+” completed when the company raised another $20 million in March 2021.

Around that time, McCullar joined OnQuality from Tolero Pharmaceuticals where, as chief operating officer, he oversaw drug discovery and development activities as well as corporate development, and commercial planning. At Tolero, he played key role in its acquisition by Sumitomo Dainippon Pharma for up to $780 million.

Earlier, he held multiple positions at Astex Pharmaceuticals—including Senior Vice President of Business Development where he was involved in the 2013 acquisition of Astex Pharmaceuticals by Otsuka Pharmaceutical for $886 million—and at SuperGen, where as Vice President of Development and Operations he led the FDA approval of the chemotherapy drug Dacogen® (decitabine) indicated for treatment of myelodysplastic syndrome.

“For maybe 15 or 16 years, I’ve had an interest in supportive care, and didn’t really understand why it was such an overlooked space,” McCullar recalled. “When the opportunity came around and I started to think more about unmet medical needs and just, how much patients suffer from these toxicities and hear from Hong and the co-founders of the unmet medical needs and their commitment to do something about it, I found it quite compelling.”

With McCullar based in Seattle, OnQuality is expanding its U.S. team, where its clinical development effort is based, with plans to grow its commercial staff there as well. The company employs 25–30 paid full-time employees with consultants and operations in China, the U.S., and Australia.

“For us to grow, that’s going to be more in the R&D side: How do we accelerate the development of these programs, to get them to the clinic and to patients? Ultimately that’s the number one goal,” McCullar said. “Secondly, we’ll be doing some more headcount increases around the G&A [general and administrative] space. We’re quite thin on the G&A side. Almost all of our employees are focused on research and development.”

OnQuality has also expanded its presence into Australia, which has sought to encourage earlier-stage clinical trials through policies such as R&D tax incentives, faster regulatory reviews and decisions, strong patent protection, and the harnessing of the country’s network of universities, independent medical research institutes, clinical trial networks, biobanks, and CROs.

“We want to be a global company,” Hong said. “We feel that medicine should not have borders, so we tried to leverage the collaboration between U.S. and China, maybe other parts of the world to use the talent, wherever it’s possible or available.”