Shedding light on the Recent Fuss about RAS, Prescient released AusBiotech Presentation

ASX listed health care stocks

With a focus on addressing mutations causing cancer, Prescient Therapeutics Limited (ASX: PTX) develops personalised medicines as potential novel cancer remedies targeting an array of debilitating cancers with significant unmet need.  Prescient has a deep product pipeline with two primary drug candidates, PTX-100 and PTX-200.

Prescient Therapeutics has recently released AusBiotech Ras Presentation regarding the latest fuss about RAS mutation in the market.

Why is everyone talking about Ras mutations?

Ras mutations have recently gained remarkable global attention, post the release of the latest data on Amgen’s new cancer drug AMG-510, a KRAS inhibitor. Let us have a look at the recent trending headlines.

Source: Company Presentation

Understanding Ras mutation

Ras is the first human cancer-causing gene (oncogene) that was discovered 37 years ago in 1982. The mutation caused by Ras gene; Ras mutation remains to be the most common type of mutation with 3 million new cancers detected with Ras mutations every year. It is estimated that over 30% of all human cancers are driven by mutant Ras proteins, including 95% of pancreatic cancers, 45% of colorectal cancer, 35% of lung cancers. Ras is one of the major growth switches found in malignant cells which, when turned on sends growth signals to the cancer cells leading to uncontrolled growth.

It is important to note that mutant Ras tumours are often unresponsive to existing therapies and till now, there are no approved treatments available that target Ras.

Ras – is it still the undruggable target?

There are several reasons why, despite the importance of targeting Ras, it is still the undruggable target. These include- various diverse categories of Ras mutations, Ras protein being smooth has no apparent binding pockets, Ras in its mutated state is very similar to normal Ras. Also, Ras does not exist externally; rather, it occurs within the cells, hence not accessible to antibodies for binding.

Prescient’s innovative PTX-100 and its unique mode of action disrupting the Ras pathway

Since targeting Ras directly has proven elusive, Prescient has discovered a unique way of disrupting the Ras pathway downstream with its novel drug PTX-100 by inhibiting the post-translation modification of Rho, Ral, and Rac where Rho is required for their activation. A first in class compound. PTX-100 inhibits geranylgeranyl transferase (GGT) which is a main cancer growth enzyme playing a vital role in cancer cell transformation. Subsequently, RhoA has become a target of interest.

Mode of action of PTX-100. Source: Company Presentation

It is noteworthy that PTX-100 is the only Ras pathway inhibitor in an ASX-listed company and to Prescient’s knowledge, the only RhoA inhibitor in clinical development across the globe. 

Competitive edge over Prescient’s peers: PTX-100 addressing many different Ras mutations

There exist three types of Ras proteins KRAS, NRAS & HRAS, each one has various different mutations that cause different cancers.  Prescient’s PTX-100 is well-differentiated over other competitor drugs as the Company believes with its unique mechanism, it targets all K-Ras and N-Ras mutant cancers while its competitor drug addresses one very specific kind of Ras mutation; KRAS G12C, as depicted in the figure below.

Different type of Ras Proteins driving different mutations. Source: Company Presentation

A glance at Listed Ras Competitors

Positive Market reactions over Ras developments

In June 2019, post-release of ASCO data, the stock prices of Amgen (NASDAQ: AMGN) reached at its peak at US$ 211.90, escalating by over 27%.

Amgen (NASDAQ: AMGN) Daily Chart (Source: Thomson Reuters)

Interestingly, on the day of Amgen’s news announcement, the share price of a small-cap company Mirati Therapeutics (NASDAQ: MRTX), that is pursuing similar technology saw its shares open gap up by 25%. Further, its share price appreciated by ~ 65% to US$111.99 in the subsequent months with a market capitalisation of US$3.0 billion.

Mirati (NASDAQ: MRTX) Daily Chart (Source: Thomson Reuters) 

Prescient’s PTX 100 Phase 1b trial

Prescient’s Phase 1b trial is a PK/PD “BASKET” study which is currently underway in Australia with an aim to determine the optimal dose and treatment schedule of PTX-100 in a hematological and solid malignancies such as myeloma, T-cell lymphomas, gastric and pancreatic cancers. This study is being conducted under the guidance of Professor H. Miles Prince, AM, a globally renowned oncologist. The readouts are expected in 2H 2020. The Phase 1 trial of PTX-100 has been previously completed and it was found to be well-tolerated and achieved stable disease.

Potential for Shorter Developmental Path

In view of the significant unmet need, it is likely that only one pivotal trial might be required post successful Phase 1b trial paving a faster path to commercialisation. “Loxo-style” Basket heme and/or basket solid cancers enriched for RhoA & Ras mutation. Despite small patient population, PTX-100 has large potential market value.

Source: Company Presentation

Overall, PTX-100 is positioned uniquely in hot Ras space with potential competitive advantages over peers’ approaches. The trial is well funded which is backed by life-science focused funds in the United States and Australia. Moreover, PTX-100 has an added exposure to the upside with PTX-200.

With a market capitalisation of $18 million and 394.26 million outstanding shares, PTX was trading at $0.049, up 6.5% on 11 November 2019 (AEST: 1:37PM).


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