Prescient Therapeutics (ASX: PTX) had a solid FY23 that has set the stage for a pivotal year to come. Front and centre of the company’s aspirations is commercialising their targeted cell therapies, primarily PTX-100. The announcement of a complete eradication of cancer in two patients, together with longer-than-expected durability of responses, has the asset shaping up to be a game changer for T-cell lymphoma (TCL), an area of oncology with a sizable and under-served target market. 

A final data readout from the recently expanded Phase 1b trial is due next quarter, which will be followed by a much larger Phase 2 trial, with the potential for that trial to serve as an approval study. In a landscape where currently available therapies for TCL are typically characterised by a high occurrence of serious toxicities, low response rates (less than 30%) and a short duration of responses (3-4 months) – there have been no serious adverse events related to PTX-100.

Of Prescient’s diverse pipeline of cancer treating assets spanning targeted therapies and cell therapy platforms, PTX-100 has the shortest path to market. FDA allowance of the Phase 2 trial as a registration study would be a major milestone for the company, opening up a rapid pathway to commercialisation.

Peripheral T-Cell Lymphoma treatment and response

There are around 5,600 PTCL cases per year in the US, and the disease has an average 5-year survival rate of 32%. Approximately 68% of patients relapse after treatment or are refractory (resistant) to conventional chemotherapy, making them eligible for therapies such as Folotyn – which costs more than US$840,000 per year of treatment.

The 3,808 odd patients for which chemotherapy did not work start their Folotyn journey with a prognosis that is quite dire, with a median overall survival rate of just 5.8 months. The drug comes with a greater than 70% chance of a serious adverse event, and is an extremely expensive but unfortunately only option for many of these people.

At the time of it’s approval in 2009, Folotyn was the only approved therapy for relapsed or refractory (R/R) PTCL. Perfectly characterising the desperation of the disease’s clinical landscape, which is still very much present today, the drug was given approval based on its overall response rate (ORR) – not clinical benefits such as an improvement in progression free survival (PFS) or overall survival (OS), which were not demonstrated.

While the FDA rushed the drug to market, there were 10 votes in favour and 4 against -.with one of the opposers being Mikkael Sekeres, who at the time was Professor of Medicine, Director of the Leukaemia program, and Vice Chair for Clinical Research at the Cleveland Clinic Taussig Cancer Institute in Ohio. Three years later, the European Medicines Agency rejected Folotyn, and the drug was issued with a negative opinion by majority vote. The regulatory agency asserted that a positive benefit-risk was not established. 

The same year, in Australia, the Therapeutic Goods Administration also rejected proposed approval of Folotyn. It managed to gain approval by appealing to the Administrative Appeals Tribunal, but for similar reasons to the FDA approval – ORR, not PFS or OS, and the persistent overarching theme of there being no treatments for PTCL other than chemotherapy and in a small portion of cases, stem-cell transplant.  Folotyn was added to the Pharmaceutical Benefit Scheme (PBS) in 2018, and now costs Australians, 440 of whom are diagnosed with PTCL annually, around $30 per round of treatment.  In the US, Folotyn costs US$842,585 per patient, per year. 

Almost a decade later, there have been several additional approvals, each with considerable toxicities, and the disease is still considerably underserved.  PTX-100 is positioned to become a safer, more effective therapy. 

Targeted therapy PTX-100 explained

PTX-100 is a first in class compound that blocks an important cancer growth enzyme known as geranylgeranyl transferase-1 (GGT-1). This disrupts oncogenic Ras pathways by inhibiting the activation of Rho, Rac and Ral circuits in cancer cells which leads to apoptosis (death) of the cell. 

RAS is a gene family that consists of 36 human genes, the discovery of which fundamentally transformed the understanding of cancer biology. While RAS genes are a normal part of the human genome, they have the ability to transform normal human cells into cancerous ones if their gene function becomes mutated. More than 30% of all human cancers, including 95% of pancreatic cancers, 45% of colorectal cancers, 35% of lung cancers and 15% of acute myeloid leukaemia – are driven by mutations of the RAS family of genes.

Mutant RAS proteins have been notoriously difficult to treat, partly because they are a defective intrinsic enzyme activity that have so far, for the most part, been virtually ‘undruggable’. PTX-100’s ability to block GGT-1 is an exciting clinical development, and is believed to be the only GGT-1 inhibitor in the world that is in clinical development. It has been granted Orphan Drug Designation by the US FDA specifically for its potential to treat TCL.

Cell therapy platforms: CellPryme and OmniCAR

Outside of Prescient’s personalised targeted therapies PTX-100 and PTX-200, the company has two cell therapy platforms which aim to overcome the challenges of CAR-T therapy. 

Prescient’s cell therapy enhancement platform CellPryme is working to solve a key problem in CAR-T. Current therapies are making too many effector and effector memory T-cells, when they need to be making more stem and central memory T-cells (Tcm).

CellPryme complements OmniCAR and has two distinct components which can be used seperately, but have distinct synergies when used together. 

CellPryme-A is an adjuvant therapy provided to patients that boosts tumour killing and host survival of conventional CAR-T cell therapies. It achieves this by overcoming the tumour’s hostile microenvironment and significantly enhancing the expansion CAR-T cells within the host. 

The platform’s benefits are even greater when used in conjunction with PTX’s CellPryme-M, which enhances adoptive cell therapy performance by shifting T and natural killer (NK) cells towards a central memory phenotype. It’s a 24-hour, non-disruptive process during cell manufacturing that improves T cell persistence, and increases their ability to find and penetrate tumours.

Prescient’s OmniCAR platform is also aiming to address key challenges of current generation CAR-T therapies by making treatments safer, more effective, more affordable and longer lasting.  The OmniCAR platform gives clinicians unprecedented control over T-cells – allowing oncologists to switch them off once they’re infused to immediately stop treatment.

Critically, OmniCAR can be efficiently armed with at least three different binders at any one time, which is crucially important when targeting cancers with multiple antigens – such as tumours. 

Technology from the world’s leading cancer centers 

Prescient’s diversified pipeline of later stage and emerging assets were developed by and with world-class collaborators including Yale, the University of Pennsylvania, the Moffitt Cancer Centre and the Peter MacCallum Cancer Centre. 

Each of Prescient’s assets is at a different stage of advancement and has the potential to be licensed by third parties, collaborated on or commercialised in-house by Prescient. The potential for PTX-100 to move into an accelerated registration study would be a game changer for the company, opening the door to a rapid commercialisation opportunity.

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