12 Aug Top 5 Companies exploring potential of Gene Expression and Pathway Signalling in the Ovarian Cancer Therapeutic Space
The American Cancer society estimates that in 2019, there will be around 22,530 new diagnoses of Ovarian Cancer and 13,980 women will succumb to the disease. It is the fifth largest cause for death in women, with over 1 in 78 chances of acquiring this disease during one’s lifetime.
The risk factors include menopause-related hormone therapy, obesity, delayed pregnancy, fertility treatments, and a family history; lynch syndrome, inherited BRAC genetic mutations to name a few. Currently there are no definitive screening tests available for ovarian cancer, which acts as an impediment for early detection and treatment. TVUS (transvaginal ultrasound) and CA-125 blood test are used to detect ovarian cancer, but are unreliable and ineffective.
Surgery is the recommended treatment option, as it helps in staging and debulking. Other treatment plans include chemotherapy with a combination of drugs, targeted therapy, and hormone or radiation therapy. However, these come with a plethora of side effects such as toxicity, hypersensitivity, hemorrhagic cystitis, neuropathy, alopecia and ototoxicity, peripheral organ damage, infertility and in some cases can even lead to second cancers.
According to a report by Grand View Research, the global ovarian cancer drugs market is expected to reach USD 4.5 billion by 2022, growing at a CAGR of 23.7%. A rising geriatric population coupled with improper lifestyle habits is fuelling the growth in the market. Scientific advancements such as non-platinum based PARP inhibitors, VEGF inhibitors, and development of biologic or small molecule therapies are changing the treatment landscape. We take a look at some companies that are leading the innovation bandwagon in this area.
Aravive, Inc (NASDAQ: ARAV)
Market Cap: $77.96M; Current Share Price: 6.23 USD
Data by YCharts
Aravive’s lead candidate for the treatment of Ovarian Cancer is AVB-500, an ultra-high affinity decoy protein that binds to GAS6 and inhibits the GAS6/AXL signalling pathway, which is primarily responsible for cell migration in cancer and fibrosis. The company announced preliminary data from an ongoing Phase 1b/2 trial of AVB-500 in patients with platinum-resistant recurrent ovarian cancer, which showed a significant anti-tumor activity. It is intended to be used either as a standalone therapeutic or in combination with other anticancer therapies.
The focal point of Aravive’s research is GAS/AXL signalling pathway, which has shown to fuel cell migration in cancers, in addition to contributing to disease progression and mortality.
The company’s novel approach targets the GAS6 ligand as against the traditional approach of focusing on the AXL signalling molecule, which has led to multiple failed attempts owing to undesirable side effects and inability to suppress the affinity of GAS6 to AXL. In fact, in preclinical studies, AVB-500 has demonstrated a 200-fold higher affinity for GAS6, thereby making it an ideal candidate for disrupting the AXL/GAS6 pathway.
The company has plans to extend the application of AVB-500 to other indications such as kidney fibrosis and IgA nephropathy.
As per its Q2, 2019 financial results, cash and cash equivalents were $48.4 million as of June 30, 2019.
Syros Pharmaceuticals (NASDAQ: SYRS)
Market Cap: $416.86M; Current Share Price: 8.80 USD
Data by YCharts
The company’s core area of interest is controlling and regulating gene expression, so that novel therapeutics can be created with the help of its proprietary gene control platform. With the help of its path breaking platform, it is able to identify disease-causing genes and develop therapeutics to control them, thereby addressing the need for a cure for disease, which were hitherto sidelined for drug discovery and development, owing to a poor understanding of their gene expression.
SY-1365, its lead candidate for the treatment of ovarian and breast cancers, is a first-in-class potent and selective inhibitor of the cyclin-dependent kinase 7 (CDK7). It is currently undergoing phase I clinical trials to study its efficacy and safety. In preclinical trials, it has demonstrated an increased biological activity, a strong anti-tumor activity with complete regressions, lowered uncontrolled cell cycle progression and lowered expression of cancer causing genes.
In addition, its pipeline consists of SY-1425, a first-in-class oral selective retinoic acid receptor alpha (RARα) agonist for the treatment of acute myeloid leukemia (AML), which is currently undergoing phase 2 clinical trials. SY-5609, an oral l CDK7 inhibitor is undergoing preclinical studies for treatment of Cancer, while the company is also focused on discovering candidates for Sickle Cell disease and Myeloproliferative neoplasms.
Syros has a worldwide strategic collaboration and option agreement with Incyte Corporation (NASDAQ: INCY), for discovering and developing up to seven novel therapeutic targets for myeloproliferative neoplasms (MPNs).
Innovation Pharmaceuticals (OTCQB: IPIX)
Market Cap: $27.80M; Current Share Price: 0.1440 USD
Data by YCharts
Innovation Pharmaceuticals lead candidate Kevertin, is a small molecule that activates p53 transcription factor that promotes apoptosis, and acts as a tumor suppressor by controlling cell mutations. Most cancers irrespective of their location and origin are characterised by a dysfunctional p53 pathway, thereby hindering the body’s natural defence against tumors.
The company has concluded an open-label Phase 2a trial for the treatment of Platinum-Resistant/Refractory Ovarian Cancer. Preliminary data suggests that Kevetrin can modulate p53 protein, possesses a strong bioavailability profile, and has a short half-life, making it suitable for oral administration either in single or multiple doses. The FDA has granted Kevetrin an Orphan Drug Designation for Ovarian, Pancreatic cancers and Retinoblastoma, in addition to being granted a rare paediatric disease designation for childhood retinoblastoma.
Furthermore, the company has completed phase I clinical trials for advanced solid tumors with positive results with respect to tolerability and therapeutic response. Kevetrin enjoys patent protection for the method of its use.
Additionally the company is developing Brilacidin, modeled on Host Defense Proteins (HDP) and the lead drug candidate for a range of indications including Oral Mucositis in patients with Head and Neck Cancer (HNC), in Ulcerative Proctitis/Ulcerative Proctosigmoiditis (UP/UPS) administered with water in an enema.
The company has entered into a series of strategic collaborations such as a licensing agreement with Alfasigma SPA for Brilacidin and an agreement with BDD Pharma to develop a tablet for targeted oral delivery of Brilacidin to the colon.
Sellas Life Sciences Group (NASDAQ: SLS)
Market Cap: $37.31M; Current Share Price: 0.1651 USD
Data by YCharts
The company is evaluating the efficacy and safety of Galinpepimut-S, in combination with Nivolumab (Opdivo), a PD-1 immune checkpoint inhibitor from Bristol- Myers Squibb (NYSE: BMY), in a Phase 1/2 clinical studies in patients with recurrent Ovarian, Fallopian Tube or primary peritoneal cancer. The results show that Galinpepimut does not add any significant toxicity burden, thereby meeting the primary endpoint of a safe combination. In addition, the 1-year landmark progression-free survival (PFS) rate showed a significant improvement at 70% from the historical rate of 43-50% in patients who received greater than 2 doses of galinpepimut-S and nivolumab.
Galinpepimut-S has previously demonstrated a strong potential owing to WT1 antigen, a transcription factor, showing an expression in ovarian cancer, which the company is aiming to target. Its approach involves using T Cells formed by combining galinpepimut-S and nivolumab to focus on the WT1 antigen. Additionally, the company is conducting multiple clinical trials involving Galinpeptimus-S in areas such as Acute Myeloid Leukemia, Malignant plural mesothelioma and multiple myeloma.
The company is working in collaboration with Memorial Sloan Kettering Cancer center to develop ground breaking immunotherapies to treat a wide variety of cancers. Its galinpepimut-S, its lead candidates for various immunotherapies, consists of four peptide chains, with two of them having a strong immune response (CD4+/CD8+) against the WT1 antigen, the most commonly found cancer antigens in multiple oncology indications.
Salarius Pharmaceuticals, (NASDAQ: SLRX)
Market Cap: $22.37M; Current Share Price: 5.97 USD
Data by YCharts
A biotechnology company focused on oncology, with special emphasis on gene expression of dysfunctional genes that contribute to cancer and its progression, Salarius is primarily developing therapeutics for treatment of hormonal cancers such as ovarian, prostate, breast cancer and leukemia. The company recently concluded a merger with Flex Pharma (NASDAQ: FLKS), collaborating on its clinical pipeline which focuses on rare, orphan cancers.
Seclidemstat, a differentiated, reversible inhibitor of the lysine-specific demethylase 1 enzyme, or LSD1, is its lead candidate for treat of a range of diseases such as Ewing sarcoma, and is currently being evaluated in a Phase 1 dose escalation/dose expansion study, expected to conclude in 2020. Next in line are additional clinical studies in solid tumors such as Ovarian, Prostate and Breast Cancers.
The company has been awarded the New Company Product Development award, encompassing a 3-year $18.7 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) and works in tandem with organizations such as the National Pediatric Cancer Foundation.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
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