PD1 and the fight to tackle solid tumours in cancer patientsAs...

PD1 and the fight to tackle solid tumours in cancer patients

As you are by now aware there are several FDA approved PD-1 therapies on the market. The cost of production and therein administration to patients renders many of these drugs cost prohibitive for many. Perhaps more importantly many are hampered by the noticeable side effects accompanying such treatment.

	Name	Target	Approved
1	Nivolumab	PD-1	2014
2	Pembrolizumab	PD-1	2014
3	Atezolizumab	PD-L1	2016
4	Avelumab	PD-L1	2017
5	Durvalumab	PD-L1	2017
6	Cemiplimab	PD-1	2018
7	Dostarlimab	PD-1	2021
8	Retifanlimab	PD-1	2023
9	Toripalimab	PD-1	2023

That said the results for these PD1 immunotherapies have been shown to be better than the standard of care (SOC) of the day. As an example in the phase 1 GARNET trial, dostarlimab or Jemperli as it is marketed shrunk tumors in 41.6% of patients across all dMMR tumor types, with the median response lasting 34.7 months. Among the responders, about 95% were still in remission after six months or longer. In the non-endometrial cancer cohort, the response rate was 38.7%. Similarly results for Mercks PD-1 drug Keytruda demonstrated a 39.6% response rate across dMMR/MSI-H tumors in its own early stage trial. About 78% of patients enjoyed responses of at least six months. Yet while mAbs to CTLA-4 and PD-1/PD-L1 have produced remarkable and durable responses in a subset of patients, the majority of patients (i.e.,between 70 and 80%) receiving anti-PD-1 therapy (nivolumab/pembrolizumab) remain resistant to monotherapy due to the complexity of resistance mechanisms and will not respond or will relapse, leaving a substantial unmet medical need.

Working in a similar vein to Jemperli and Keytruda the Professor Kauyama designed PD1 Vaxx was licensed by Imugene in an attempt to reduce the cost and side effects associated with PD1 treatments. Espousing the virtues of combination therapies Professor Kauyama in 2019 combined his PD1 vaccines with Her 2 vaccines to examine whether he could obtain higher efficacy in syngeneic Balb/c models. PD1-Vaxx was combined with his B-Vaxx (combo HER-2). Results illustrated PD1-Vaxx outperformed the industry-standard mouse anti-PD-1 antibody in a mouse model of HER-2-positive CRC. Combined triple vaccination (PD1-Vaxx and B-Vaxx) was more effective in the CT-26/HER-2 carcinoma cell line in syngeneic Balb/c that exhibited superior activity compared with the positive gold control antimouse PD-1 (CD279) mAb.

Moving away from PD1 and combination immunotherapies for a moment we find Imugene conducted a Phase Ib clinical study of its HER-Vaxx anticancer vaccine in gastric cancer patients overexpressing HER-2 target protein. Imugene Ltd’s HER-Vaxx is a B-cell peptide cancer vaccine designed to treat tumors that over express the HER-2/neu receptor, such as gastric, breast, ovarian, lung and pancreatic cancers. This small study data in 68 patients showed a 100% objective response rate in three patients who received the optimal dose of 50 μg. Many onlookers of Imugene have long suggested Imugene should conduct a combination study between Professor Kauyama’s PD1 Vaxx and Professor Wiedermann’s Her Vaxx, based upon empirical evidence produced in these 2019 trials.

Professor Pravin Kauyama

In February of this year when taking on the role of new role as the Vera Bradley Foundation Professor of Breast Cancer Innovation and director of the Immuno-Oncology and Vaccine Immunotherapy laboratory at the Brown Center for Immunotherapy, PD1 Vaxx founder Pravin Kauyama was asked what he was most proud of. He noted his recent work in the field of immuno-oncology, where he was developing vaccines for several checkpoint inhibitors. He went on to say his PD-1 vaccine (PD1-Vaxx) successfully completed a Phase I clinical trial and is now enrolling patients with a combination of our PD1-Vaxx and ROCHE’s drug atezolizumab (TECENTRIQ®). Late last year I understand a large investor in Imugene (IMU - ASX) wrote to the company's shareholder enquiry email asking when an update on the company's PD1 Vaxx Tercentriq Trial would be forthcoming. Apparently the email was responded to by Imugene’s Dr Nick Ede with the answer “soon”. An interesting response given we are now half way through the following year with still no response on this much heralded clinical trial.

Just as Pravin Kauyama is working on the development of PD1 vaccines in combination with HER 2 therapies to combat patients with metastatic and recurrent solid tumors, he is ascertaining how their combinations might be used in various cancers. Alongside Professor Kauyama Imugene are developing oncolytic viruses in combination with PD1 Mab’s and T cell therapies to target solid tumours that have metastasised within patients. Late last year Imugene announced one such virus, Vaxinia, had proven successful in triggering immune responses with 6 out of 7 gastrointestinal participants in a Phase 1 dose escalation trial for the drug. Like the aforementioned PD1 Vaxx Tercentriq combination trial IMU shareholders have been awaiting date from the Vaxinia Trial since late October. The cynics among them point to the fact they may have to wait until late October this year, prior to the company's next AGM, for further promising data to be cherry picked. That being the time when investors are set to vote on the boards next round of remuneration.

Given the size and scope of the PD1 market, the need for safe and low cost vaccines such as PD1 Vaxx, it is unfortunate Imugene’s business personnel have been unable to garner the interest of a Big Pharma participant to put down a significant upfront payment to license the drug, either with or without its potential combination partner Her Vaxx. The outcome would surely offer IMU holders the promise of ongoing royalties, something they are unaccustomed to at this stage of their investment in the company. Managements ability to convey clear and succinct messaging surrounding the number of patients dosed in trials such as their PD1 Vaxx Tercentriq trial, in addition to their lack of commercial outcomes for their B cell immunotherapies, is undoubtedly weighing heavily on their share price performance. At this stage of the company's development it is not advisable to take the stage suggesting data is good, without producing the said data referred to. Nor is it suitable to infer you are conducting clinical trials in line with Big Pharma protocols, only producing data at the completion of a clinical trial, where primary endpoints have been met. In this day and age the market demands information, otherwise it breeds fear among investors, as opposed to greed. Investors simply become scared of the unknown and begin to find other homes for their hard earned investment dollars. Homes where company CEO’s discuss such topics as the market size for their biotech products, in addition to expected commercial outcomes in dollar terms.

I sincerely hope Imugene management can bring some clarity to the table with respect to the aforementioned clinical trials for their novel immunotherapies long prior to this years AGM, for not only investors sake, but for their own. For a company that represents such esteemed talent as Professors Fong, Kauyama and Wiedermann surely its time to finally put one if not two of their shots on goal in the back of the net. If not shareholders are set to be asking management, or at worst replacing them, with someone who can. In my opinion Imugene (IMU - ASX) possesses undoubted value for cancer patients and investors alike. Now is the time to capitalise on it.

Best of luck to ALTH’s

DYOR Seek investment advice as and when required Opinions only