Canada’s Tetra Bio-Pharma is on a path to become a world leader in the development of cannabinoid-derived medicines, with several promising drugs undergoing advanced clinical trials. Tetra CEO Dr Guy Chamberland said from his Montreal office that his company’s goal is to derive cannabinoid-based medicines using scientific methods and the safety data required to commercialise products for the pharmaceutical industry; and that the company already has several candidates in the pipeline.
The Tetra Bio-Pharma product which is closest to market, said Chamberland, is CAUMZ™, a synthetic inhaled cannabinoid pain relief drug designed to complement existing pain relief medicines such as opioid derived therapies, including Fentanyl® and morphine lines. It is currently undergoing Phase 3 trials in the United States and Canada in a study titled ‘SERENITY ©’; and Tetra hopes to obtain regulatory approval by late 2021.
CAUMZ delivery and indications
CAUMZ is delivered to patients using an inhaler called the Mighty Medic, which is a device created by Storz & Bickell, a wholly owned subsidiary of Canopy Growth. The device is currently approved for use in Canada and is under review by the US Food and Drug Administration (FDA) as part of the approval process for CAUMZ.
Chamberland is optimistic about the potential that cannabinoid-derived drugs like CAUMZ could be used as alternatives to highly addictive opioids. He noted that their drug is not an analgesic, but that it instead affects how the brain perceives pain so that the patient is not as impacted by it as before. “Because [the pain] doesn’t bother you anymore, you don’t need as much opioids as you did before and I think that’s the biggest breakthrough,” he said, adding it would also reduce the need for opioid-taking patients to take additional antidepressants and hypnotics, which are regularly prescribed to treat the side effects of depression and insomnia that come with chronic pain.
Tetra has also released new information on its drug development programme for CAUMZ following a Type B meeting with the FDA, announcing that the first indication for CAUMZ will be contributing to the care of cancer cachexia patients. These individuals suffer from an incurable and malignant form of cancer which is refractory to treatment; so the aim is to prolong their survival and improve their quality of life. Given that health regulators understand the dire consequences for patients with certain life threatening conditions where there is no effective treatment available, Tetra expects to obtain a Fast Track designation in order to speed up the review of CAUMZ.
In addition to the potential use of CAUMZ as a pain relief drug, Chamberland said that Tetra Bio-Pharma recently received FDA Orphan Drug Designation for THC in the treatment of hepatocellular carcinoma. The company will leverage the pharmacokinetic and safety data from its CAUMZ Phase 1 clinical trials to support its Phase 2 trial of a modified formulation of CAUMZ, under the name HCC 011, in patients with advanced hepatocellular carcinoma, a common form of liver cancer. Tetra intends to initiate this new trial in 2020.
“We are thrilled that we can bring this new cancer therapy to Phase 2 clinical trials with no additional drug development costs,” Dr Chamberland noted. “The CAUMZ kit technology already exists, so we will maximise our investment in the development of inhaled cannabinoid drugs to bring another drug to the market.”
Tetra Bio-Pharma in 2020
Chamberland sees the year ahead as being a big one for Tetra, as the impending FDA approval of the company’s first drug will transform it from a biotech focused on research to a pharma company which manufactures and distributes commercial products to the medical community.
“One of the biggest mistakes I’ve seen among biotechs is they don’t prepare for the commercial world,” said Chamberland, noting that Tetra will be ready; as its senior management has years of experience in the pharmaceutical industry with expertise in sales execution, marketing, market access and commercial compliance aspects.
Chamberland added that joint ventures and partnerships are a big part of Tetra’s growth strategy both for distribution and manufacturing, but also for strengthening their product pipeline.
“Our vision has always been to partner with big pharma,” he said. “Obviously, these companies proceed slowly because it’s a question of assessing the risk to bring these drugs to the market. As we progress in moving them forward, closer to drug applications, I think this will be a catalyst for increased discussions.”
Co-operation and collaboration
One example of such a deal is when Tetra Bio-Pharma and Altus Formulation Inc signed a joint venture agreement last spring under which the two companies would work together under the joint name TALLC to develop a series of cannabinoid receptor-targeted therapeutics addressing areas of high unmet need, specifically in the fields of pain, oncology and ophthalmology.
Another example came in the autumn when Tetra announced CB2 Therapeutics, a joint venture with Thorne Research Inc and Onegevity Health, which will combine Tetra’s expertise in cannabinoid research with Thorne’s robust distribution network and Onegevity’s data-driven microbiome platform in order to target diseases caused by chronic inflammation.
Another of Tetra’s cannabinoid-derived drugs currently undergoing Phase 1 clinical trials in the US, and which will soon enter into a Phase 2 trial titled PLENITUDE ©, is QIXLEEF™, an inhaled cannabinoid medicine that is being tested for the treatment of uncontrolled pain in advanced cancer patients. Unlike CAUMZ, which is based on a synthetic cannabinoid, QIXLEEF is a botanical product that uses dried flower buds. While this may conjure up the impression that plant-based raw materials are simple to work with, the notion of biological variability is a serious concern. This is why receiving FDA validation of Tetra’s scientific approach makes the company well primed for the global QIXLEEF market penetration.
According to Allied Market Research, the global drug market for pain management was about $60bn in 2016 and is estimated to reach $130bn by 2023. This includes pain medications for indications such as arthritic pain, neuropathic pain, cancer pain, chronic back pain, postoperative pain, migraines, and fibromyalgia.
Given this huge market, Tetra’s CEO believes that QIXLEEF can be developed for pain indications beyond cancer and be used as a second- or third-line drug for use in pain relief, adding that the company is accelerating plans to sign a commercial partner in the United States for the distribution and sale of the drug. Further approval for additional disease indications will enable QIXLEEF to compete in the $44.3bn pain relief market, which includes all first line therapies and self-care options.
A recent Letter of Advice and Type B meeting with the FDA added important information on the drug development programme for QIXLEEF and the PLENITUDE clinical trial which will evaluate the drugs’ impact on advanced cancer patients with uncontrolled pain. Based on a successful outcome, Tetra would be in a position to commercialise the world’s very first dried flower botanical cannabinoid drug product for the treatment of uncontrolled pain in patients with advanced cancer.
“In addition to addressing critical unmet medical needs for some of the most vulnerable patients, Tetra’s astute regulatory knowledge is meaningful for its shareholders. Communication from the FDA also validated Tetra’s nonclinical programme looking at pain indications apart from cancer and confirmed areas where Tetra could get a waiver for some of the nonclinical safety requirements. These waivers signify short term savings of over $5m for the first marketing application of QIXLEEF, as well as future savings,” Chamberland stated.
Addressing the opioid crisis
“Tetra will be continuing to develop QIXLEEF for advanced cancer pain,” said Chamberland, “But we will now evaluate the best market opportunity within this large potential multi-billion-dollar market of second- or third-line pain medications. If clinical trials are successful, this will significantly shift the opioid battle.”
The opioid crisis continues to devastate families and communities in Canada. From January to July 2019 there were at least 2,142 apparent opioid-related deaths in Canada, of which 90% were accidental, according to statistics compiled by the government of Canada. Of those deaths, 80% were attributed to Fentanyl or Fentanyl analogues: a substantial increase from the 55% reported in 2016.
“Our rich cannabinoid-derived product pipeline has the potential to play a major role in opioid sparing, thus addressing a societal issue of critical proportion,” said Chamberland.
While CAUMZ and QIXLEEF are the company’s most promising drugs, Chamberland said that they have at least another 10 candidates in the pipeline and some of them come from their acquisition last year of Panag Pharma. He said that his company is not averse to acquiring other companies if it will expand their product pipeline, strengthen an existing product or help them maintain their lead in the field of cannabinoid medicines, upon which they are laser focused.
Chamberland believes the true measure of a successful vertically integrated biopharmaceutical company is the presence of a rich pipeline of patent protected molecules which can become its next generation of therapeutics. This is one of the most important avenues to safeguarding the company’s assets and its shareholders’ investments. This vision recently came to fruition in the form of a co-development agreement with Boston-based MAKScientific, a recognised world leader in endocannabinoid research and drug development. The collaboration will see MAKScientific develop new small molecules, which Tetra will then validate for efficacy in managing numerous health conditions including cancer, pain and inflammation. For Tetra Bio-Pharma, this means a long runway with patented new cannabinoid-derived drug candidates for the company to develop after CAUMZ and QIXLEEF have received their marketing approval.
“I have been in the pharma industry for more than two decades,” wrote Chamberland in a year-end message to colleagues and investors. “It is a manic business. The good news is that the highs and lows are wrapped up with the greater purpose we all serve in finding solutions to meet significant, unmet medical needs, not the least of which is debilitating pain. This is something our entire team is passionate about.