The famous businessman and billionaire Lucio Tan once said, “Everything is for sale at the right price”. And working on that assumption, let’s take a deeper dive into Imugene’s B cell platform, and the potential sale of that asset. Keeping in mind, (as I noted in my previous post), Big Pharma has a keen eye on anything at the moment that can lengthen their patent runway, reduce drug costs and increase their market share.
Let’s recap for the sake of repetition just what Imugene’s B cell platform is all about.
As you would be aware the platforms drugs have been specifically constructed and designed to engage ones immune system and therein assist in the fight against cancer.
Assuming a sale is on the cards (or at the very least a licensing/partnership deal), the first item for sale in Imugene’s B cell platform is their drug known as Her Vaxx. Her Vaxx was invented by Dr Ursula Wiedermann from the Medical University in Vienna, together with a research team of scientists based at that location. Most recently in a Phase 2 trial for the drug, (for whichrecruitment was completed in January 2021), the important clinical endpoint of Progression Free Survival (PFS) has been met. The statistically significant required number of PFS events has occurred and data from these 24 events has now been analysed with the final Overall Survival Rate (OFS) readout expected within months.
Imugene managing director and CEO Lesley Chongs goal for her company is to collect the data and produce really good medicines for patients. In April 2021 she announced to the ASX “I am delighted to report that we have achieved this new significant milestone for patients with advanced gastric cancer, following on from the important interim data released in 2020 and new data presented at AACR earlier this month.” Yet at the time in an interview on Proactiv Investors as a percursor to whether her drugs, including Her Vaxx, would progress to Phase 3 trials she noted, “The beauty is in combinations. If we have a safer, kinder drug, that exhibits similar levels of efficacy, we become this beautiful partner”.
Consequently in recent announcements Imugene has stated three more Phase 2 trials are soon to commence. Two of which are said to be in combination with existing drugs. One can only assume these being with drugs currently produced and distributed by either a Big Pharma or larger bio pharma entity.
Following Lucio Tan’s aformentioned analogy that everything is for sale at the right price, the second drug that could potentially be for sale in Imugene’s B cell platform is the drug known as PD 1 - Vaxx. Pravin T.P. Kaumaya, currently Professor of Medicine at the Ohio State University Medical Center in Columbus Ohio and Director of the Division of Vaccine, is the inventor of Imugene’s B cell vaccine known as PD1-Vaxx. In 2018, Imugene Limited, negotiated two exclusive licenses containing rights to 10 of Professor Kaumaya’s patents, a purchase that encompassed his entire body of B-cell cancer vaccine inventions. In 2020, the U.S. Food and Drug Administration granted investigational new drug approval (IND) for clinical testing of PD1-Vaxx. The B cell vaccine has shown to be well tolerated and capable of generating sustained anti-HER-2 immune response compared to monoclonal antibodies, to which most patients develop resistance. Studies indicate peptide vaccination may help patients avoid therapeutic resistance and may offer a promising alternative to such monoclonal antibodies as Herceptin and Perjeta.
In SYDNEY, Australia, on 27 August 2021 Imugene in an announcement to the ASX themselves stated clinical results continue to indicate that PD1-Vaxx is showing early signs of an immune response in patients, with antibodies to the target biomarker PD-1 evident in validated assays. Imugene MD & CEO Leslie Chong said at the time “Phase 1 trials are generally designed to look for safety, tolerability and early response signals to determine the optimal dose for further development. The completion of the monotherapy component of our Phase 1 trial will be a milestone for Imugene and clinicians treating Australians faced with the challenges of lung cancer.”
In ongoing studies, Imugene in collaboration with Kaumaya have developed a PD-L1 vaccine (PD-L1-Vaxx) that, when combined with the B-cell epitope-specific vaccine B-Vaxx, shows synergistic activities. They have developed several syngeneic cancer models to test their various combination immunotherapies. Finally, they are developing vaccines for CTLA-4, TIM3, LAG3 and TIGIT that will form a combination immunotherapeutic platform for developing cancer cures. These studies in addition to Wiedermans Her Vaxx, form the nucleus of what we refer to as the Imugene (IMU) B cell platform.
Most noticeably PD1 has been trialled (preclinically in mice) in combination with Her-vaxx and the result was positive. "The anti tumor effect of our Her-2/neu vaccine (HerVaxx)62,63 was shown to be potentiated when combined with JT-mPD1.39,”Prof Wiedermann and her colleagues stated in the October edition of ESMO Open - the journal of the European Society for Medical Oncology ("An online-only, peer-reviewed oncology journal dedicated to publishing high-quality medical research and educational content from all disciplines of oncology, with a focus on innovative clinical and translational cancer research.) This recent announcement increases the potential of a sale of Her - Vaxx in combination with Imugene’s PD1 - Vaxx. The fact the drugs in combination have trialled well preclinically is a boon for any incoming Big Pharma suitor. Unfortunately for them they’re now going to have to pay an even higher price if they want the “clean sweep” including both Her Vax, PD1 (and associated B Vaxx affiliates). Keeping in mind both drugs have extensive patent lives.
So you have two drugs (and several more in the B cell pipeline at Imugene) that are assisting end stage cancer patients with progressive cancers such as gastric and lung cancers, both of which are in many instances incurable. You have one drug Her - Vaxx that has effectively extended life against the standard of care (chemotherapy), and another PD1 - Vaxx, that has illicited early signs of an immune response in patients. In other words at low dosage rates it has reduced if not eradicated the end stage lung cancer patients tumour. Yes both drugs have been shown to be safe. Yes the inventors, Big Pharma and/or existing drug manufacturers see the potential in combining together to form what Imugene CEO Lesley Chong describes as “a beautiful partnership”. Hence their willingness to participate in future trials.
And why, (as I noted last week) does Big Pharma pay such huge multiples and valuations for these drugs?
Remember the majority of cancer drugs fall short, or fail to receive patents and/or regulatory approval. And even if they are approved, many can later be removed due to adverse side effects and an overall lack of safety. Big Pharma is acutely aware that Rome wasn’t built in a day, that it takes time and considerable money to develop these drugs. And for those that do succeed to reach inhuman trials including Imugenes Her Vaxx and PD1 Vaxx, the pathway is a long and arduous one. Take Imugenes development as a case in point.Imugene began as a research project in the laboratory of Professor Ursula Wiedermann at the Medical University of Vienna. Over the nine years from 2004 Wiedermann developed a B cellpeptide cancer immunotherapy that could induce an antibody response targeting HER-2 overexpressing tumours. That’s right, 2004, 17 years ago. Similarly Professor Kaumaya and his colleagues at the Ohio State University began animal (mouse studies and trials) on T and B cells in the early 1980’s. That’s right over 40 years ago! As we now know their studies ultimately found that PD1-Vaxx was effective in inhibiting tumor growth. And yes they were even more effective when used in combination with a second therapeutic peptide vaccine, one that targets two sites on the HER-2 receptor on colon cancer cells. The combination treatment produced complete responses in nine of 10 animals. That vaccine, called B-Vaxx, is still being developed and trialled by Kaumaya and Imugene, all these decades later.
Yet the “fly in the ointment” for Big Pharma lies in the fact they don’t have time to develop drugs. They don’t have decades. Their shareholders want results, and they want them now. And its not just shareholders, the Feds are now on their back demanding less expensive drugs. Time is running out, their drugs are costly and rife with side effects. The search for safe and efficacious drug combinations is the path of least resistance when it comes to saving their skins.
So what does a potential sale really offer Imugene shareholders?
Well for starters it doesn’t matter whether the IMU share price is 1 cent of $1 when a sale announcement is made, you’re going to be looking at dollars not cents from that point on. In the interim the fact both Her - Vaxx and PD1 - Vaxx have trialled succesfully on their own and in combination with one another is exciting for all involved. Whilst we do not know the outcome of the two independent trials, or indeed what the outcome of a combination (in human) trial of both drugs would yield, we do know Big Pharma have recently paid large sums for drugs that have exemplified successful results in much smaller demographics than those targeted by Imugene’s B cell platform. As an example in September Merck & Co. announced it has agreed to buy Acceleron Pharma for $11.5 billion. The deal sent a signal to the biotech market Merck is willing to spend more than usual to diversify its business beyond the cancer drug Keytruda. Based in Cambridge, Massachusetts, Acceleron specializes in developing medicines for uncommon diseases. It has one product, Reblozyl, which is approved by the Food and Drug Administration to treat a group of bone marrow cancers as well as anemia associated with the blood disorder beta thalassemia. The company is also working on an experimental drug, sotatercept, for a rare and potentially life-threatening type of high blood pressure in the lungs called PAH, or pulmonary arterial hypertension. Having suffered from high blood pressure myself, and hypertension, I am excited by the prospect of such a drug, and the potential it has to assist more advanced patients than myself. Yet I note that PAH is a rare condition, with about 500-1000 new cases being diagnosed each year in the U.S.
Conversely I make note of the fact that HER-Vaxx is a B-cell immunotherapy designed to treat tumors that over-express the HER-2/neu receptor, such as gastric, breast, ovarian, lung, and pancreatic cancers. This is a large demographic. Similarly PD1 - Vaxx has the potential to be ultimately effective in treating not only non-small cell lung cancer, but melanoma, hodgkin lymphoma, bladder cancer, kidney cancer and even breast cancer. You are right in concluding these are not rare disorders effecting small sections of the population. As an example gastric cancer is one of the most common cancers, whilst lung cancer remains the leading cause of cancer death, with an estimated 1.8 million deaths in 2020 alone. So yes, when Professor Kaumaya’s PD1 Vaxx Phase 1 trial results are released for Cohort 3 patients in the coming weeks, if successful (as anticipated), the stakes are up there with space travel.
All quiet on the Western Front
Given what’s at stake perhaps there is a reason the board at IMU has gone “all quiet on the western front”, as it were. Holding your cards close to your chest and not exuding any excess hubris, or sense of exuberance, are all in a days work for experienced bio pharma players such as Axel Hoos, Imugene director and major player in their B cell platforms rise to prominence in the field of cancer research. When biotech firms such as Imugene and Big Pharma are in discussions they tend to ask themselves many questions. Should they bring to a halt all communications with the investment community or move forward with limited interaction? Should they answer only fact-based (or historical) questions or avoid inquiries altogether?
The recent silence at times appears deafening doesn’t it. No word on PD 1 Cohorts 1 and 2. Or PD1 Cohort 3 for that matter. No announcement of the aforementioned publication in ESMO Open. IMU usually reports on Cancer Conference presentations and publications does it not? The silence surrounding corner stone investors. Do they have a role to play in the future? Are they here to stay or fly by nighters? No idea as to the identity of the Her Vaxx combination partners in future Phase 2 trials? Are they big name players or big name punters?
Unfortunately shareholders knowing the answers to these questions is not relevant to the outcome of trials nor the future success of the company. The not knowing merely serves to give us yet more sleepless nights. Was Dr. Monil Shah employed in June simply to bolster Imu’s bank balance through a pending capital raise, or to oversee an already existent big pharma deal? Why did Axel Hoos leave GSK a month later? And why did Dr Russel sell those shares? And then there’s the trolls, with their pithy one liners and unsubstantiated claims. Attempting to feast on the carcass of the golden goose before it lays the golden egg. Akin to hyenas at the feet of the Lion King. And what for the protagonists, yeah of little faith? Baying for Chongs blood as they pray for her Last Supper, as opposed to our Christmas Feast. Songwriter Colin Hay puts it down to Overkill. Worrying over situations that I know will be alright, Its just Overkill. More days awaiting the IMU announcements that never appear on our computer screens the morning therafter.
Yet rest assured each and every Imugene director, not the least Lesley Chong, have the best interests of shareholders and prospective cancer trial patients at heart. They themselves are shareholders. They have experienced cancer in their lives through friends and relatives. They themselves work with cancer patients, day in and day out, striving to achieve worthwhile outcomes for them and their families.
Given the recent need to respond to the ASX on August 23 of this year following an ASX “please explain” letter sent to the IMU Board (i.e, after comments made in an article earlier that month), it’s no wonder IMU are tending to err on the side of caution. And if they are in fact in negotiations with a Big Pharma suitor, confidentiality and indeed privacy may limit their propensity to report. “Keep your mouth shut or the whole deals off”, is a phrase that springs to mind. “Loose lips sink ships” is but another. The IMU board don't want to do anything that could kill the golden goose. And despite the background noise this is not in any way contrary to the need for continuous disclosure. For it’s not until a deals all but done the company need report (see exception to Rule 3.1A - if the information concerns an incomplete negotiation or proposal).
That said either way I sense the end is nigh for Imugene’s B cell in it’s current form. Imugene’s Chairman Paul Hopper has said on more than one occasion he is not in the business of taking their drugs to market and into production. He suggests that more often than not these drugs are sold at or nearing the end of Phase 2 trials. And realistically speaking what more does Big Pharma wish to see? They knew in April Imugenes B cell platform was safe, efficacous and exhibiting an immune response in patients.In short the combinations with their existing drugs abound. Let alone the potential of an Imugene owned Her Vaxx, PD1 Vaxx (or B Vaxx) combination. Not to mention the lower cost to produce and administer drugs responsible for firing up the immune system, warranting reduced levels of care and treatment over time.
Have the trials been successful, or failed at the final post? Is there a B cell sale in the offing? A partnership afoot? A license deal in the making? Or is Imugene going to fly on solo?
Your guess is as good as mine. None of us know or can begin to know the outcome of Imugene's current trial results or the potential discussions and negotiations eminating from them. We can merely hypothesize at this moment in time. Wait in eager anticipation of “what might be”. But that said my moneys on an announcement before the AGM on November 19. And I’m thinking in that announcement the IMU board is going to entice us to follow more than just the science. We may indeed be following our dance partner all the way to a Christmas party. And a Christmas Party much larger than the one anticipated when Paul Hoppers golden goose was first on the IMU menu late last year.
Do your own research and seek investment advice.
(20min delay)
