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OnQuality’s chief medical officer and co-founder Hong Tang discusses the firm’s pipeline of cancer supportive care drugs.

The oncology space is one of the largest hotbeds for drug development and innovation, and in the past few decades, a spate of new and effective cancer therapies have come to market.

While these treatments are often extremely powerful and can be life-saving, they aren’t without their downsides. Many of them cause adverse reactions and side effects that are very hard on the patients already battling cancer.

Some of these side-effects are so severe that certain patients cannot tolerate them, leading to them reducing the dose or halting treatment altogether.

Unfortunately, innovation in cancer supportive care doesn’t measure up to the innovation in cancer drug development. There are very few approved drugs available for the myriad side effects experienced by cancer patients in treatment, some of which occur in around 50% of patients.

One company dedicated to relieving these symptoms and improving cancer patients’ quality of life is OnQuality Pharmaceuticals, a start-up established in 2019 with a presence in both the US and China. The firmhas five cancer supportive care drugs in its pipeline, one of which is already in Phase II clinical trials.

Clinical Trials Arena sat down with OnQuality’s chief medical officer and co-founder Hong Tang to find out more about its lead candidate, OQL011, and the other treatments it is developing for various cancer drug side effects with a large unmet need.

Hong Tang: At OnQuality we chose to focus on cancer supportive care drug development, as it is an area that has really lagged compared to cancer drug development. We have seen a lot of new innovative therapies developed in the past ten to 15 years for cancer, such as targeted therapy, immunotherapy and biologics, however, supportive care has not been developed as much or hasn’t been paid attention to. We not only want the patient to fight cancer, but at the same time, we want to take care of them while they are fighting it.

Our lead compound OQL011 is in the oncodermatology space. It’s a topical treatment for moderate to severe hand-foot skin reaction (HFSR), a common side-effect for patients treated with vascular endothelial growth factor receptor (VEGFR) inhibitors used for various kinds of cancer including kidney cancer, liver cancer and thyroid cancer.

With HFSR, the hands and feet develop, rashes, peeling, swelling or even blistering which can be very painful and sometimes patients have to stop the treatment as a result. Treatment options are very limited and there are no regulatory approved drugs in the space. Often physicians have to prescribe moisturiser, urea cream or even topical steroids, but there is no definitive evidence that those would work.

OQL011 is developed with the mechanism of the cancer drug in mind, meaning that we specifically target the drug mechanism to try to overcome its effect on the hands and feet and at the same time preserve the anti-cancer effect. That is why we focused on making it a topical treatment, so it wouldn’t interfere with the anti-cancer treatment.

KP: Can you give us some details on the Phase II trial of the candidate? How is it going?

HT: Currently, OQL011 is in a Phase II double-blind, placebo-controlled multicentre study in the US. Enrolment should be finished by the end of summer. OQL011 was eligible for the US Food and Drug Administration (FDA) 505(b)(2) regulatory pathway for existing or repurposed drugs, so we could go straight to Phase II and skip earlier clinical phases as the safety is already well known. Hopefully, this means we can shorten the development journey and get the treatment to patients faster.

The study is ongoing in 15 sites. These include top academic centres such as Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, Northwestern and Yale University and the Dana Farber Cancer Institute, as well as community centres such as the Innovative Clinical Research Institute and Montefiore Einstein Center for Cancer Care in The Bronx.

We try to have a combination of academic and community centres so that we reach a varied geographic patient population.

KP: What are some of the other most difficult side-effects cancer patients in treatment face with an unmet need?

HT: Before targeted therapy we had chemotherapy. Most people know the side effects of chemotherapy – nausea, vomiting, diarrhoea, even hair loss or low blood count. With targeted therapy, people somehow thought there might be fewer side effects, but in reality, there are just different side effects that are very common and include mouth ulcers, rashes and diarrhoea.

Because the mechanisms are different, the treatments are often different from the agents approved for cancer chemotherapy. For example, we have diarrhoea medication for chemotherapy-induced diarrhoea, however, the targeted therapy-induced diarrhoea does not respond to those anti-diarrhoea drugs well. This means that there is an unmet need there for patients on those therapies.

KP: What are the cancer therapy-induced dose-limiting toxicities where treatment gaps exist that you have identified?

HT: There are two main toxicities that we have identified. One is skin toxicity. There are now some centres that have doctors focused on diagnosis and management of skin toxicity in cancer patients relating to cancer treatment – it’s a new discipline called oncodermatology.

The other main area is gastrointestinal (GI) toxicity, so that’s mainly oral and intestinal mucositis, diarrhoea, mouth ulcers and rash. GI toxicity not only comes from targeted therapy but also immunotherapy. Work done in this area is what we call oncogastroenterology.

KP: What is the market opportunity to address a highly unmet medical need such as side effects suffered by patients on anti-cancer treatment?

HT: Well, I hope good medicine is good for the market. Speaking from the medical point of view, first of all, there are no approved drugs in this area. The reality is that patients who cannot tolerate the side effects of a cancer therapy have to switch to another treatment, lower the dose or stop the treatment altogether. So, I feel the medical need is tremendous in that area.

We don’t want a patient to run out of cancer therapy options and there are limited therapies available, so we want to provide treatments to mitigate the side effects so patients can stay on cancer therapy. In our trial, we ask patients to stay on the cancer therapy while treating the side effects.

KP: OnQuality recently announced the closing of its Series A+ financing round bringing the total raised to$35 million – how do you plan to use these funds?

HT: Mainly for the development and advancement of our lead candidate OQL011 and for our other candidates further down the pipeline.

We have two other compounds in oncodermatology. OQL033 is for chemotherapy induced-hand foot syndrome. We completed pre-IND with the FDA for this candidate last year. The other is OQL023 for epidermal growth factor receptor (EGFR) inhibitor-induced rash which mainly occurs on the face, upper chest and upper back. Being so visible this side-effect is very bothersome to patients, so we’d like to rapidly move forward with the drug development of that candidate too.

We also have two other candidates in the discovery phase both in the oncogastroenterology space – OQL041 for EGFR inhibitor-induced diarrhoea and OQL051 for chemotherapy-induced diarrhoea.

We also are looking into ways to prevent hair loss, as right now there is no specific FDA approved drug for the prevention of chemotherapy-induced alopecia. If we could come up with a medication or topical treatment for that, we could prevent cancer patients from having to go through the emotional turmoil of losing their hair.

On Tuesday, the All India Institute of Medical Sciences (AIIMS) in Patna started clinical trials of India’s homegrown Covid-19 vaccine Covaxin in children between the ages of two to 18 years old.

The vaccine, developed by Hyderabad-based Bharat Biotech in association with the Indian Council of Medical Research, is to be tested in a paediatric population of 525 subjects in Phase II/III clinical trials.

The trial will take place at various sites across India. As well as at AIIMS Patna, studies will be conducted at the Prakhar Hospital in Kanpur, Mysore Medical College and Research Institute (MMCRI) in Mysuru, Pranaam Hospital in Hyderabad, and Meditrina Institute of Medical Sciences in Nagpur.

 

Participants will receive two doses of Covaxin administered at a 28-day interval.

The trial commenced with the vaccine being administered to three volunteers aged 12-18 years.

“We are commencing the trials today in the reverse order of age from today. Children in the 12 to 18 years age group will be given the shots first. We will then proceed with the six to 12 years age category before inoculating children in the two to six years age bracket,” said professor of community and family medicine and the principal investigator of the trial at AIIMS-Patna, Dr CM Singh according to Hindustan Times.

Singh also said that not all registered participants will receive the vaccine – only those who test negative for Covid-19 or who have not had the virus previously will receive a dose.

“Besides physical examination of the child, we will conduct real-time polymerase chain reaction (RT PCR) to check them for Covid antibody and test them for any pre-existing diseases before administering the vaccine,” he said.

Covaxin received the Drugs Controller General of India (DCGI) nod to conduct paediatric clinical trials on May 11. The trials come just in time, as concerns around how certain Covid-19 strains will affect children grow. 

“The new form of Corona that came to Singapore is being said to be extremely dangerous for children, in India it may come as a third wave. My appeal to the central government: one, air services with Singapore to be cancelled with immediate effect. Two, priority on vaccine options should be worked out for children, too,” Kejriwal said.

Most countries are yet to approve any vaccine for use in children. Last month, the EU, US and Canada authorised Pfizer-BioNTech’s vaccine for use in children aged 12-15. The vaccine has also just been approved in the UK for the same age group.

Vaxxas, an Australian clinical-stage biotechnology firm spun out of the University of Queensland, has announced promising results from pre-clinical trials into its novel high-density microarray patch (HD-MAP) for vaccination against Covid-19.

A novel SARS-CoV-2 spike subunit vaccine was dry-coated onto the HD-MAP patch using proprietary systems and technology developed by the company. The patch uses an ultra-high density 9-by-9 mm array of tiny projections that are invisible to the naked human eye to deliver the drug. It comes packaged in a hockey-puck-shaped applicator with a foil seal and is applied to the skin to deliver the vaccine to the abundant immune cells found directly below the skin surface.

The pre-clinical study of Vaxxas’ HD-MAP demonstrated enhancement of immune response compared to vaccination by traditional needle-and-syringe, including significantly enhanced T-cell and spike-specific antibody responses when compared to needle-and-syringe delivery.

The same impressive protection against Covid-19 was not seen with the same vaccine when delivered via injection, even when the spike subunit vaccine formulation included appropriate adjuvants.

Once the vaccine dose was applied on the Vaxxas HD-MAP patch it was shown to be stable for at least 30 days at 25˚C. This means that the patch has the potential for unrefrigerated distribution in the future and potentially self-administration.

“We designed this research to address the serious on-going need to improve the global vaccination efforts against Covid-19 and future pandemics. Based on our results, we believe that Vaxxas’ HD-MAP could offer a compelling solution that importantly could use less vaccine and potentially could be readily distributed without refrigeration for self-administration,” said University of Queensland research fellow David A. Muller, the leader of the study.

“This combination could make the HD-MAP extremely well suited to support the massive need for global population vaccination and, indeed, we believe that HD-MAP offers a superior alternative to conventional needle-and-syringe.”

Muller and his team also found that while the SARS-CoV-2 spike subunit vaccine used on the patch was designed based on the molecular spike structure inherent to the Wuhan-Hu-1 reference strain, post-vaccine serum antibody levels “clearly demonstrated the potential to potently neutralize emerging isolates”. This includes those from the UK strain (B.1.1.7) and the South African strain (B.1.351) and potentially others.

“We are extremely excited about these compelling early results showing the potential of Vaxxas’ proprietary HD-MAP vaccination platform to deliver safe and effective vaccines against Covid-19,” said Vaxxas president and CEO David L. Hoey. “We believe that having a single-dose vaccine that could be easily distributed and self-administered would greatly improve global pandemic vaccination capabilities.”

The research underlying the study was co-funded by Vaxxas and the Queensland Government and performed in collaboration with researchers at the University of Queensland and Griffith University.

Vaxxas isn’t the only firm exploring alternative delivery methods for Covid-19 vaccines. Vaccine patches are also being developed by similarly-named Cambridge, Massachusetts biotech Vaxess Technologies and at Swansea University.

Dr Anthony Fauci said his country is eager to involve Indian investigators in global clinical trials to evaluate the safety and efficacy of Covid-19 therapeutics

America’s top infectious disease specialist Dr Anthony Fauci on Thursday said his country is eager to involve Indian investigators in global clinical trials to evaluate the safety and efficacy of COVID-19 therapeutics.

The National Institute of Allergy and Infectious Diseases has a long history of collaboration with its counterpart agencies in India, Dr Fauci said during a conversation organised by the US-India Strategic and Partnership Forum.

The partnerships between the NIH and India’s Department of Biotechnology as well as what the Indian Council of Medical Research have helped produce important scientific and public health discoveries in the past.

I am confident they will continue to do so in the future. India’s contributions to global scientific knowledge are well known to all. With strong governmental support and a vibrant biopharma private sector, this knowledge already is yielding solutions to COVID-19 prevention and care, Dr Fauci said.

India’s Ambassador to the US Taranjit Singh Sandhu said as India ramps up vaccine production to cater to its needs and those of the world, it relies on the support of the United States in ensuring raw materials and component items are available in good supply.

Vaccinating the world is our best bet against another wave of the pandemic, and the ideal way to speed economic recovery, he said.

Observing that India-US health collaboration is not new, he said under the longstanding Vaccine Action Programme between both nations, they developed a vaccine against rotavirus, which causes severe diarrhea in children.

Indian companies have also manufactured, highly cost-effective HIV drugs for use in African countries, building on cooperation between US organisations and the private sector, he said.

Looking ahead, we need to invest in preparing for the future. Future global resilience will depend on how well prepared we are in dealing with future pandemics. We need to work to further expand our bilateral programmes in areas such as epidemiology, digital health and patients’ safety to tackle communicable, and non-communicable diseases and improve infectious disease modelling, prediction and forecasting.

Similarly, the sharing of clinical expertise, standards, and experiences of hospitals, in the management of infectious diseases, especially COVID-19, would add to the knowledge base, Sandhu said.

I think it’s important to understand when the US went through a crisis last year, it was India which kept up to support the US from critical medicine. And India is going through his own challenges us stepped up. So, it is a reciprocal partnership, USISPF president Mukesh Aghi said.

Sandhu said last year, as the pandemic hit, India ensured the integrity of health supply chains, providing essential medicines to the US.

This year, when the US supported India during the second wave, President Biden recalled India’s help. Companies such as Gilead and Merck present here today have been critical in supplying essential medicines to India which has helped us fight the pandemic and saved innumerable lives, he said.

Guangzhou Link Health Pharma and George Clinical have signed a term sheet to enter a strategic agreement to launch a clinical development company to deliver trials.

The new independent joint venture company called Link-George Clinical Research will deliver clinical trials for Link Health and associated firms with which it has signed licensing deals.

Link-George plans to commence six clinical trials this year and this is anticipated to develop with the expansion of Link Health’s in-licensed portfolio.

George Clinical CEO James Cheong said: “We are very excited to enter into this joint venture with Link Health as part of a novel platform providing a one-stop service for in-licensing, clinical development, marketing authorisation and commercialisation.

Link-George will merge the expertise of Link Health and George Clinical to accomplish increased efficiency and provide more value across a set of services from pharma licensing to project delivery.

The company offers deep knowledge in the analysis of pharma targets and consultation on pharma licensing and regulatory and commercial landscape in China.

As clinical trial professionals prepare for postpandemic operations, they see technology adoptions and hybrid protocol designs as the innovations most likely to be continued after the crisis ends.

“Anyone watching the clinical trial industry over the past year can see the changes to protocol designs, patient monitoring, auditing and even some of the endpoints for trials,” said Jill Johnston, president of Study Planning and Site Optimization for WCG, during the opening panel at the MAGI Clinical Research vConference last week. “One result of the pandemic is that organizations are beginning to embrace more resilient and often digitally enabled endpoints that support options for remote participation.”

Johnson led the conference’s keynote session during which attendees were asked to participate in a four-question poll. In the first question, 77 percent of respondents said they were moderately or highly confident that changes made to trials during the pandemic will continue.

Panelist Kathryn King, senior vice president for clinical development at Aptinyx, remarked at how quickly the barriers to enacting changes to traditional trials — both real and perceived — fell once the pandemic hit. “There weren’t any other options in terms of how we were going to keep going,” she said. “A lot of the things that got put in the way previously just fell to the wayside. It wasn’t a matter of change agents finding ways over or around them.”

Now it’s a matter of keeping up the momentum, King said. “We have to carry forward. The ability to fail and learn something, the ability to keep going even when it’s challenging, the ability to celebrate successes and carry those successes forward — that’s what we have to do.”

In the poll’s second question, respondents said technology adoption is the top activity most likely to continue postpandemic though that was closely followed by protocol designs with more hybrid visit options.

“We often joke that [the clinical trials enterprise] is a bit of a Frankenstein right now,” said Karri Venn, president for research at LMC Manna Research. “We’re deploying different technologies and piecing it together to benefit patients the most, but to also make it user-friendly for [site] staff. We want to make sure that we’re having some optimization when we deploy technology in clinical trials, so we definitely have a lot of work to go through.”

In the poll’s third question, respondents said the top challenge confronting decentralized trials is changes required to standard procedures and processes.

Much like the struggle to understand how to use real-world data in clinical trials, the best uses of decentralization will take a while to iron out, Venn said. “But getting to specific endpoints, not just collecting a lot of data, and what you do with that data, is going to be important. There’s a world of opportunity here.”

On the fourth poll question, respondents said greater participation in clinical trials and reduced costs were the top two benefits of decentralized trials.

Venn acknowledged that replacing a traditional study with a completely virtual study would save on some costs. But, she said, there are additional costs that come with making such a change. “We’ve deployed a 100 percent paperless system and that came with cost, both with the actual technology itself … as well as the teams that we had to kind of create to implement the change.”

“We’re now actually coming together with different sites that are using the same technology to talk about workflow optimization and best practices so that we can see what’s the gain for the site,” she said. “But right now, it’s debatable.”

Consolidation among big CRO players is continuing to churn.

Following a Wednesday afternoon report from the Wall Street Journal saying a deal was close, Thermo Fisher has announced plans to acquire PPD for $17.4 billion. WSJ had reported that the parties could wrap up an agreement as soon as this week. It’s the second CRO M&A deal in as many months, following the Icon-PRA Health Sciences deal in late February.

Thursday morning, Thermo Fisher announced the transaction would account for $17.4 billion in cash plus an assumption of about $3.5 billion in net debt. That total represents a per share price of $47.50, good for a 24% premium on PPD’s closing price from Tuesday afternoon.

In a statement, Thermo Fisher CEO Marc Casper said:

Pharma and Biotech is our largest and fastest growing end market, and our customers value us as a strategic partner and an industry leader. The acquisition of PPD is a natural extension for Thermo Fisher and will enable us to provide these customers with important clinical research services and partner with them in new and exciting ways as they move a scientific idea to an approved medicine quickly, reliably and cost effectively. Longer term, we plan to continue to invest in and connect the capabilities across the combined company to further help our customers accelerate innovation and drive productivity, while driving further value for our shareholders.

In the wake of WSJ’s report, PPD $PPD shares rose 12% before the market closed Wednesday afternoon, and it was up another 3% after hours. Thermo Fisher’s stock $TMO had largely been down for the day and closed down 1.4%.

As part of the merger there were lots of cost “synergies” that Thermo Fisher plans to realize — likely resulting in significant cuts over the next three years. Thermo Fisher said it plans to save $75 million over that time period from cuts. They also expect an additional $50 million in “revenue-related synergies.”

Thermo Fisher is hardly new to these types of deals, coming a long way from its start as an R&D instruments and materials company selling things like lab equipment. Back in 2017, Thermo Fisher bought Patheon — a major contract manufacturer — to start providing clinical trial services and logistics.

Then last month, the company dropped $600 million to shore up its manufacturing supply chain in the wake of a sharp rise in Covid-19 work. Funds were directed toward its short-term Covid-19 projects and more than double its capacity for the future.

Though taken private about a decade ago, PPD went public again in February 2020 in a $1.62 billion IPO that at the time was the largest of the year. The company had been looking to capitalize not only on an increase in outsourcing and R&D spending, but growth in the biotech sector as a whole.

Most of the IPO funds went toward redeeming bonds, which were issued in a recapitalization project engineered by its biggest private equity backers in 2017, its S-1 said. In addition to its role as a CRO, PPD also offers laboratory services.

Shares of FibroGen were crashing this morning after the company unsuccessfully attempted to express confidence in the benefit/risk profile of its anemia drug, Roxadustat. This comes ahead of the U.S. Food and Drug Administration’s review of the company’s New Drug Application following a data clarification it made regarding its efficacy. 

After announcing Tuesday that the FDA tentatively scheduled a Cardiovascular and Renal Drug Advisory Committee to review roxadustat, San Francisco-based FibroGen sought to quell any investor concern by providing what it called “clarification of certain prior disclosures” of primary cardiovascular safety analyses from the roxadustat Phase III program that were submitted to the FDA in the NDA. FibroGen is developing roxadustat for the treatment of anemia of chronic kidney disease (CKD).

Enrique Conterno, chief executive officer of FibroGen, said the company became aware that primary cardiovascular safety analyses included post-hoc changes to the stratification factors. In the company’s announcement, Conterno said analysis of the data may show that roxadustat is not superior to another drug called epoetin-alfa in lowering the risk of cardiovascular events in some kidney disease patients. 

According to company data, the analyses with the pre-specified stratification factors result in higher hazard ratios and 95% confidence intervals. For MACE+ in dialysis and for MACE and MACE+ in incident dialysis, the 95% confidence intervals include 1.0. While these hazard ratios remain below 1.0, based on these analyses the company said it cannot conclude that roxadustat reduces the risk of (or is superior to) MACE+ in dialysis, and MACE and MACE+ in incident dialysis compared to epoetin-alfa.

FibroGen was quick to note that the additional analyses do not change its assessment that roxadustat is comparable to placebo in non-dialysis dependent patients and to epoetin-alfa in dialysis dependent patients using MACE to measure cardiovascular safety. Contera emphasized the company maintains its confidence in roxadustat’s benefit risk profile.

The company also said that there is no change in the underlying roxadustat data or to the efficacy analyses from the Phase III program. FibroGen added that it has begun a comprehensive internal review to ensure such issues do not occur in the future.

Roxadustat is the first in a new class of medicines, HIF-PH inhibitors that promote erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin. The medicine has already been approved in China, Japan and Chile for the treatment of anemia of CKD in adult patients on dialysis and not on dialysis.

FibroGen is also assessing Roxadustat for anemia associated with myelodysplastic syndromes and for chemotherapy-induced anemia. The company is working in collaboration with Astellas and AstraZeneca on the development and marketing of roxadustat.

AzurRx BioPharma has started its Phase II clinical trial to evaluate micronised oral niclosamide tablets, known as FW-1022, in patients with Covid-19 gastrointestinal (GI) infection.

Patient enrolment for the Phase II two-part, two-arm, placebo-controlled RESERVOIR clinical trial is expected to begin this month, with topline data anticipated in the first quarter of next year.

The study has two primary objectives which will confirm the safety of the prescription small molecule drug niclosamide to treat patients with Covid-19 GI infection. They will also demonstrate efficacy in clearing the SARS-CoV-2 virus from the GI tract.

The rate of fecal SARS-CoV-2 virus clearance assessed by RT-PCR, comparing the niclosamide arm to the placebo arm for up to six months, forms the primary efficacy measure of the RESERVOIR trial.

These long-term observation data could indicate that treatment with niclosamide can potentially improve ‘long haul’ symptoms related to Covid-19.

Global contract research organisation PPD will manage the trial.

AzurRx BioPharma chairman, CEO and president James Sapirstein said: “For many, the after-effects of Covid-19 can be as bad as the disease itself, and this includes a growing number who experience severe GI complications due to what many believe is the ability of SARS-CoV-2 to hide in reservoirs within the GI tract.

“We believe micronised oral niclosamide has the potential to target SARS-CoV-2 directly in the gut and, doing so, become an important addition to the armamentarium of therapeutics that will unfortunately be required by many who contract Covid-19.”