Good post @egosbar and I to am looking forward to the results of...

Good post @egosbar and I to am looking forward to the results of Imugene's recently announced Phase 2 PD1 Vaxx Trial. But there is much to digest in what is an already competitive space.

Being a big fan of PD1 Vaxx and Professor Kaumaya, the B cell vaccines inventor, I was pleased to see this weeks announcement Imugene is preparing 10 clinical trial sites in Australia and the UK for a new PD1-Vaxx Phase 2 colorectal (CRC) cancer clinical trial set to begin in 2024. That said, l do think PD1 Vaxx is starting well behind the eight ball here, and without a Big Pharma partner, may never catch up, in what is an extremely competitive marketplace. Since Tesaro sold to Glaxo Smith Kline (GSK) in early 2019, Dostarlimab, a leading drug in the colorectal cancer space, has performed a number of expansive, well funded clinical trials, resulting in drug approvals within several indications now, within a matter of a few years. Whilst having received some flack recently for suggesting Imugene is moving too slowly and should consider out licensing or indeed selling some of their artillery to increase speed to market with larger trial sizes, I would draw your attention to Dostarlimab’s previous owner Tesaro’s sale to GSK. The sale highlights what can happen when Big Pharma, as opposed to a smaller player such as Tesaro, gets hold of a good thing such as Dostarlimab, in the oncology space.

Dostarlimab Background

(Courtesy of https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433597/)

Cancer is nothing but uncontrolled cellular growth. When this uncontrolled cellular growth takes place in colon or rectum area, it is termed as colorectal cancer or simply colon cancer .The epidemiology of colorectal cancer may change drastically depending on geographical locations. It is the second and third most prevalent type of cancer in females and males respectively. Incidence and mortality rates of this type of cancer is significantly lower in females than males. Dostarlimab (brand name JEMPERLI) is a collection of laboratory-synthesized molecules which can act as substitute for human antibodies Dostarlimab is an antibody to anti- programmed cell death receptor-1 (PD-1) which is used for the treatment of adults with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors as well as dMMR-recurrent or advanced cancer in endometrium.

JEMPERLI attaches to PD-1, found on the surface of T cells. PD-1 in healthy T cells acts as a brake that prevents the cells from starting an uncontrollable immune response.

GSK and Dostarlimab

Glaxo Smith Kline (GSK) acquired Dostarlimab (marketed as Jemperli) through the purchase of Tesaro for $5.1 billion USD back in December 2018. At the time GSK CEO Emma Walmsley noted “The acquisition of TESARO will strengthen our pharmaceuticals business by accelerating the build of our oncology pipeline and commercial footprint, along with providing access to new scientific capabilities. This combination will support our aim to deliver long-term sustainable growth and is consistent with our capital allocation priorities. We look forward to working with TESARO’s talented team to bring valuable new medicines to patients.”

Since acquiring Dostarlimab GSK has performed several extensive trials on the drug. Phase 1b, Phase 2 and Phase 3 trials have all been conducted in several indications including but not limited to ovarian, colon, colorectal cancer and other forms endometrial and DMMR solid tumours. On 17 August 2021 in London UK, GSK announced the second FDA approved indication for Dostarlimab, following their GARNET study which demonstrated an objective response rate of 41.6% across dMMR solid tumours. 95% of responders had a duration of response of ≥6 months. The trial administered 267 patients with recurrent or advanced dMMR solid tumours who were evaluable for safety. Researchers at the time researchers also linked dostarlimab to a 58% disease control rate; cancer vanished in 13% of patients, while 30% of patients saw some improvement. Based on the Garnet trial, dostarlimab gained accelerated approval from the US Food and Drug Administration (FDA) in April 2021, and full approval in February 20

More recently healio.com noted in an article reported a more recent Dostarlimab Study into 494 patients Dostarlimab ‘will change the lives of our patients’ with endometrial cancer. The key takeaways being the addition of the anti-PD-1 antibody to chemotherapy led to a doubling of PFS at 24 months (36.1% vs. 18.1%). Added to which researchers observed an even greater PFS benefit among women with dMMR-MSI-H tumors.

Data derived from Mirza MR, et al. Final overall survival and long-term safety in the ENGOT-OV16/NOVA phase III trial of niraparib in patients with recurrent ovarian cancer. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, Florida.

When Imugene’s PD1 Vaxx cured a patient of non small cell lung cancer for close to three years they didn’t publicise the fact in a specific article. However GSK did not stop their Dostarlimab patient stories coming out.

Check out this story in the Deccan Herald at https://www.deccanherald.com/science/ wonder-drug-cures-100-cancer-of-uk- woman-2717586#:~:text=Dostarlimab%20can%20be%20offered%20to,syst em%20in%20eliminating%20the%20cancer

UK woman cured of cancer by 'wonder drug'

The 42-year-old civil servant who was diagnosed with bowel cancer last year was given dostarlimab infusions for six months, after which tests have shown zero evidence of the disease. The article goes on to say that aside from Carrie Downey, the woman at the centre of the article, Dostarlimab was administered to 18 patients with rectal cancer last year for a total of six months, and every single one of them was showed zero evidence of the cancer at the end of the treatment.

Carrie Downey.Credit: sbuhb.nhs.wales

As reported elsewhere, a small group of colorectal patients (18 individuals) just experienced something no short of a scientific miracle, their disease subsided completely after experimental treatment conducted by a group of doctors at Memorial Sloan Kettering Cancer Center, New York.

But as Fiercepharma.com notes the PD-1/PD-L1 market is a booming competitive market segment. Sanofi and Regeneron, sixth into the field, recently showed their PD-1 inhibitor Libtayo, given alone, cut the risk of death by 43% versus chemotherapy in a 710 patient non-small cell lung cancer trial. With the FDA now weighing approval in that setting, the companies could inch Libtayo toward blockbuster territory, provided their ambitious development plan pans out. However fiercepharma.com stated in a recent article all competitors, i.e., GSK, Sanofi, BMS, Regeneron and others will still have to go up against Merck's Keytruda—the undisputed champion of the first-line NSCLC market, and a player in the endometrial cancer space, too. In September 2019, Merck and Eisai's Keytruda and Lenvima combo bagged its first approvals for certain endometrial cancers in the U.S., and Keytruda has boasted an OK since 2017 to treat MSI-H tumors located anywhere in the body.

The market in endometrial cancer is competitive too. pharmaphorum.com in October this year reported GSK has built the case for first-line use of its PD-1 inhibitor Jemperli in endometrial cancer, with new survival data that could help it expand the label for the drug. The latest readout from their RUBY trial shows that adding Jemperli (dostarlimab) to standard chemotherapy with carboplatin and paclitaxel improved overall survival (OS) compared to chemotherapy plus placebo, reinforcing earlier results showing that it extended the time to disease progression or death. There are approximately 60,000 cases per annum in this cancer indication and according to the company’s global head of oncology R&D, Hesham Abdullah, RUBY is the first immunotherapy combination study to show a survival benefit in this setting. Though AstraZeneca Imfinzi (durvalumab) and Merck (Keytruda) are already making waves with endometrial cancers.

So where does the Dostarlimab, Libtayo, Imfinzi and Keytruda developments leave Imugene and PD1 Vaxx? Well, definitely not in a position of strength at the moment. But PD1 Vaxx has exhibited strong safety signals in its Phase 1 trial, with the hint of efficacy at low doses, when trialled on late stage lung cancer patients. And given this gazetted trial is on earlier stage patients, at higher dose rates, it's an opportunity to visualise how Imugene’s B cell vaccines perform in patients with early diagnosis, prior to having surgery and other treatment. This could see Imugene jump a few places up the pecking order if the drug outperforms in patients with stronger levels of immunity than those administered in Imugene trials to date. Professor Kaumaya is anything but stupid, there would no doubt be a method to his madness, or rhyme to his reason, and I’d be happy to back him on in this latest strategy. Shall it be the wonder drug clinicians have likened Tesaro, sorry GSK’s Dostarlimab to? Let’s wait and see....

DYOR Seek investment advice as and when required Opinions only