Imugene’s PD1 Vaxx is often compared in Imugene ASX...

Imugene’s PD1 Vaxx is often compared in Imugene ASX announcements to the worlds best selling drug in 2023, that being Merck’s Keytruda. Let’s do some research to find out why.

PD1 Drugs

For those new to Imugene its worth noting they are developing a drug targeting PD1, similar to the worlds leading drug in 2023, that being Merck’s Keytruda. Keytruda earned a record $25 billion USD last year, making the cancer drug the biggest selling drug in the world.

So how do these so called PD1 drugs work? When PD-1 binds to PD-L1, it basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them hide from an immune attack. Monoclonal antibodies such as Keytruda, that target either PD-1 or PD-L1, can block this binding and boost the immune response against cancer cells. Imugene’s own PD1 drug is appropriately entitled PD1 Vaxx. Following a successful Phase 1 Trial administering non small cell lung cancer patients, PD1 Vaxx is now being trialled in lung and gastric cancer patients, at various sites in Australia, the US and UK.

The PD1 Market Leader - Keytruda

There are three types of cancer immunotherapy

• Monoclonal antibodies (MABs) Some MABs have an effect on the immune system. ...
• Checkpoint Inhibitors. Checkpoint inhibitors are a type of immunotherapy that block different checkpoint proteins. ...
• Cytokines. Cytokines are a group of proteins that are found naturally in the body

As mentioned above, Merck’s Keytruda is classified as a monoclonal antibody, whereas Imugene’s PD1 Vaxx is classified as a checkpoint inhibitor. In medical terminology, PD1 Vaxx is the first prototype checkpoint inhibitor B-cell epitope vaccine, exploiting future novel synergistic vaccine combinations.

In clinical terms, the interaction of PD-L1 on cancer cells with PD1 on the surface of T-cells causes cancer cells to escape from the immune system by preventing the activation of new cytotoxic T-cells in the lymph nodes and subsequent recruitment to the tumour. From a layman’s perspective drugs such as Keytruda and PD1 Vaxx are designed to prevent cancer cells escaping from the immune system, to enable ones own immune system to be recruited in the fight against cancer.

https://www.drugs.com/medical-answers/success-rate-keytruda-3555529/ notes in a recent article, the success rate of Keytruda depends upon the type of cancer you have, the stage of cancer, your previous treatments, your overall health and other factors.

Keytruda - a blockbuster drug designed to treat multiple cancer indications

Keytruda’s $25 billion USD in earnings in 2023 is due predominantly to the broad range of cancers able to be treated by Keytruda. These include both blood cancers and solid tumours and are as follows:

• melanoma, squamous cell carcinoma, or Merkel cell carcinoma (types of serious skin cancer)
• lung cancer, Non-Small Cell Lung Cancer (NSCLC)
• head and neck squamous cell cancer
• classical Hodgkin lymphoma (type of blood cancer))
• primary mediastinal large B-cell lymphoma
• cancer of the kidney, bladder, and urinary tract
• liver cancer
• biliary tract cancer
• colorectal (colon) cancer
• cervical cancer
• endometrial cancer
• advanced stomach cancer
• esophageal cancer
• triple negative breast cancer
• Microsatellite Instability-High or Mismatch Repair Deficient Cancer (cancer that affects the proper repair of DNA inside the cell)
• Tumor Mutational Burden-High (TMB-H) Cancer (cancers that have many gene mutations)
• cancers that laboratory testing proves to have certain specific DNA mutations

Keytruda - A snapshot of clinical trial successes to date

Three types of cancer approved by the FDA for Keytruda treatment are non-small cell lung cancer, advanced melanoma (a serious form of skin cancer), and bladder cancer.

With respect to Advanced non-small cell lung cancer (advanced NSCLC), in one study, half of the patients receiving Keytruda + chemotherapy were alive without their cancer spreading, growing, or getting worse at 8.8 months, compared to 4.9 months for patients treated with the chemotherapy regimen alone.

When it comes to Advanced melanoma (skin Half (50%) of the patients who received Keytruda every 3 weeks were alive at 4.1 months, compared to 2.8 months for patients receiving Yervoy. Keytruda was shown to reduce the risk of dying by 31% compared to Yervoy.cancer).

In the cancer indication of Advanced bladder and urinary tract cancer (urothelial carcinoma) Keytruda was evaluated in a clinical study of patients with urothelial cancer who had previously received a platinum-based chemotherapy regimen (KEYNOTE-045). For the patients receiving Keytruda, the chemotherapy had either never worked or stopped working. Overall, patients receiving Keytruda lived longer than those receiving chemotherapy. Patients receiving Keytruda lived for 10.3 months (median overall survival) compared to 7.4 months with chemotherapy.

The bottom line is that in general, PD-1 immune checkpoint inhibitors like Keytruda have been shown to significantly prolong overall survival (OS) in some patients with various cancer types, but Keytruda does not always work for everyone.

PD1 Vaxx - Keytruda’s pending patent expiry and the road ahead

When Keytruda's patent life expires toward the end of this decade the $25 billion USD it is making in sales each year is thrown back on the open market. In anyone’s language, that’s plenty of freight. In fact if Keytruda was just hitting the market now, and forecast to earn as it has, it would be worth close to $100 billion USD. So I guess if Imugene’s PD1 Vaxx was anywhere near as good as Keytruda, it would add approximately $21.26 to Imugene’s current valuation. If only it were that simple. Even if PD1 Vaxx is close to if not better than Keytruda in prolonging life, shrinking tumours, and reducing the incidence of death among cancer patients, it still needs to be approved by the FDA to treat multiple cancer indications. That process takes time and costs money. No doubt if successful PD1 Vaxx would be situated in touch with Keytruda, the leading drug seller in 2023, but that’s a pretty tall order. Could PD1 Vaxx be as effective as Keytruda? By all means. It works with the same medical principle as Keytruda, with possibly less side effects than Mercks’ blockbuster drug. PD1 Vaxx is being developed in similar markets to that of Keytruda, including the lucrative lung and gastric cancer indications. To assume Imugene’s PD1 Vaxx can suck up a large portion of the market left behind when Keytruda retires, is not as far fetched as it sounds.

PD1 Vaxx and Tercetriq

In a few weeks news of Imugene’s PD1 Vaxx IMPRINTER combination trial with Roche Therapeutics Tercentriq is expected. The first of what from memory promises to be 88 patients, was dosed back on June 1, 2023. Tecentriq® has previously shown clinically meaningful benefit in various types of lung cancer, with six currently approved indications in the US. Investors shall soon be able to gauge if PD1 Vaxx is up to the task of taking on Mercks older and more experienced PD1 competitor, Keytruda. I for one hold high hopes for PD1 Vaxx. With both a complete and partial responses at relatively low doses in incredibly sick lung cancer patients during its Phase 1 Trial, PD1 Vaxx already has some runs on the board. Like Imugene’s Vaxinia, its now simply a matter of sit back and wait as the science unfolds. Like Keytruda before it, Imugene’s PD1 Vaxx has the potential to swim in deep revenue pools. Imugene’s recently announced PD1 Vaxx Trial into gastric cancer exemplifies the depth of a burgeoning, cancer market. Last year, an estimated 15,713 new cases of bowel cancer were diagnosed in Australia alone, affecting 8300 males and 7413 females. It is estimated that a person has a one in 19 (5.2 per cent) risk of being diagnosed with bowel cancer by the age of 85. Like lung and the significant number of other cancer indications treated by PD1 designed vaccines such as Keytruda, Opdivo and now PD1 Vaxx, the scope for long term sales is immense. As an example colorectal, or bowel cancer is the world’s third-most common cancer, with an annual incidence of more than 1.2 million cases and a mortality rate of about 50 per cent.

AstraZeneca’s Imfinzi - A Keytruda competitor

PD1 Vaxx isn’t the only competitor moving briskly or should I say hotly onto the heels of Merck’s Keytruda. AstraZeneca’s Imfinzi (durvalumab) is but one of many challenging Keytruda’s throne. But it isn’t all cut and dried when it comes to knocking down Keytruda from their number one perch. In April last year, the British biopharma Astra Zeneca released data from their Phase III AEGEAN trial studying Imfinzi before and after surgery in patients with resectable stage II, IIIA or IIIB NSCLC. Those treated with Imfinzi showed a 32% EFS rate, compared to Keytruda’s 42% in KEYNOTE-671.

Keytruda, Opdivo and the hunt for biosimilars

Keep in mind Opdivo® marketed by Bristol Myers Squibb is similar to Keytruda in terms of safety and effectiveness, the key differences relating to their dosing frequency, the drugs they are used in combination with and the types of cancer they are approved for treating. Despite Keytruda’a success Opdivo is still right up there when earnings come to town, highlighting how much revenue their is to be eased from successful PD1 drugs. BMS' blockbuster cancer drug Opdivo generated $9bn in 2023, a 9% increase from 2022. The human IgG4 anti-PD-1 monoclonal antibody saw a label expansion, as well as increased demand from patients with gastric, bladder, non-small cell lung cancer (NSCLC) and melanoma.

With Keytruda’s patent life now running out years, the race is on the combine Keytruda with other drugs, alternatively to create biosims or biosimilars, which are similar to Keytruda in their structure and function. This isn’t exactly an easy process, for biosimilars must undergo extensive analysis to confirm they have the same characteristics as the reference biologics. pfizer.com notes that between research and development and clinical testing, studies have shown that the development of new biologics (including the cost of failures) can exceed $2 billion and can take 10 years or longer—and that's on top of developing and deploying the state-of-the-art technology necessary for manufacturing. But given patients receiving Keytruda lived for 10.3 months (median overall survival) compared to 7.4 months with chemotherapy, the existing Standard of Care (SOC), the race is on to find another blockbuster cancer drug, similar to Keytruda, to treat such cancer indications as breast and lung cancer (see above).

Keytruda combinations - The race is on

Keytruda is currently being combined in hundreds of clinical trials to treat multiple cancer types, including those expressing Her 2 positive tumours, such as those found in breast or gastric cancer. Another of Imugene’s B cell candidates Her Vaxx, developed alongside PD1 Vaxx, is currently in a combination clinical trial with Keytruda, as but one example. PD1 Vaxx itself has previously demonstrated synergistic vaccine combinations with another Imugene licensed HER-2 targeted vaccine, known as B - Vaxx, invented as well by Professor Pravin Kaumaya, at the Ohio State University of Medicine.

Does Imugene’s PD1 Vaxx hold all the answers?

Professor Kaumaya’s PD1 Vaxx may not provide the solutions for all cancer patients in years to come, though like Keytruda before it, the potential market size available within this biotech segment is, as this article exemplifies, put simply, huge. Lung, breast, gastric and ther other cancer indications treated by so called PD1 drugs, either with or without combination therapies such as Imugene’s Her Vaxx, are set to continue increasing in years to come. Unfortunately lung cancer, the indication PD1 Vaxx is currently being trialled on in combination with Roche’s Tercentriq, is set to be the worlds leading cause of cancer deaths in 2024, making the pending IMPRINTER trial results all the more important. Keep in mind it is not only Merck striving to find a replacement for the blockbuster drug Keytruda, Big Pharma companies such as Roche are well and truly in the game as well. Roche knows all to well what it feels like to see sales dwindle at the expiration of a drugs patent life. Sales of their own HER 2 drug Herceptin have fallen from a high of $6 billion US dollars in 2019, down to a figure of $2 billion USD in recent years, as the drugs patent expiry approaches.

If indeed an out licensing agreement is negotiated for Imugene’s Her Vaxx, PD1 Vaxx, or both, a combination trial between these two B cell candidates may well be on the cards. Monoclonal antibodies such as Keytruda and Opdivo are responsible for producing a large number of side effects within cancer patients. Conversely Imugene’s PD1 Vaxx and Her Vaxx have exemplary safety records.

DYOR Seek investment advice as and when required Opinions only