Clinical data focus for the smallest players

After delving into the key catalysts due for big pharma and biotech companies, here Evaluate Vantage looks at the smallest players - those with a market cap of under $1bn. Novel approaches in oncology are one focus, while underserved neurological conditions such as Rett and Angelman syndromes are another area of interest.

Notably, almost half of the companies in this list have gone public in the past two years, and the upcoming clinical readouts will provide investors with initial glimpses at whether their money was well spent.

One such company is Replimune, which completed its $101m IPO in 2018. Towards the end of this year investors will see early data from two of its oncolytic immunotherapies.

RP1, the company’s lead project, is a version of HSV type 1 engineered to replicate in tumours. RP1 is armed with two genes, one encoding a fusogenic protein to enhance cell death and the other encoding GM-CSF, a cytokine believed to aid immune activation. RP2 is a derivative of RP1 that expresses an anti-CTLA-4 antibody-like molecule.

Updated results are due from a phase II study testing RP1 and Opdivo. Earlier data from skin cancer expansion cohorts were encouraging, albeit in a small number of patients with relatively short follow-up. An objective response rate of 86% was seen in cutaneous squamous cell carcinoma, comprising four complete and two partial responses, and an ORR of 31% occurred in anti-PD-1-refractory cutaneous melanoma.

As for RP2, initial data are expected from a phase I study in solid tumours, testing the compound as a single agent and combination with Opdivo.

Another early-stage oncology player due to report data is TCR2 Therapeutics, which floated last year raising $75m. TCR2 has a T-cell receptor fusion construct (TRuC)-T technology that it claimns incorporates features of Car-T and TCR T-cell therapies.

TC-210 is the company’s most advanced project and targets mesothelin-positive solid tumours. A dose-escalation update from its phase I study is due. Interim data previously reported on five patients showed all to have tumour regression, including two with partial response, one of which was confirmed.

TC-110, meanwhile, targets CD19-positive B-cell haematological malignancies, and initial data are expected from a study including adult ALL and indolent non-Hodgkin's lymphoma, areas in which Car-T therapies are not currently commercialised.

Rare disease

Neurology also looks to be an area of interest for the smallest players. Rett syndrome is a rare neurological disorder that almost exclusively affects girls and is a target for Anavex’s therapy Anavex 2-73. Results from two phase II studies of the small-molecule activator of the sigma-1 receptor, one taking place in the US and the other in Australia, are due to report.

Earlier data from the open-label portion of the US study showed improvements in scores on both the Rett syndrome behaviour questionnaire and the clinical global impression-improvement scale at seven weeks in six adult patients. The upcoming data are from 15 patients in the placebo-controlled part of the trial.

There are no approved products for Rett and the failure of Newron’s pivotal study in May left a thin pipeline, with Avanex one of the most advanced of those still standing. The ultimate treatment goal would be a disease-modifying approach, but this are still some way off. Novartis’s gene therapy AVXS-201 is not expected to start trials until 2024.

Anavex 2-73 is also being tested in Parkinson’s disease dementia. The 120-patient study is measuring two different doses versus placebo. Primary and secondary endpoints will assess cognition and parkinsonian motor symptoms and sleep function during the 14-week study.

Another condition with a lack of treatment options is Angelman syndrome, a complex genetic disorder that primarily affects the nervous system. The most advanced clinical candidate is Ovid’s OV101, also known as gaboxadol.

The primary endpoint of the pivotal Neptune study of OV101 is CGI-I-AS, a clinical global impression improvement score at 12 weeks, with the study 95% powered to show a 0.8-point improvement from baseline on the aggregate measure of these scores.

Despite meeting the CGI endpoint in the phase II Stars trial, OV101 failed to show a benefit on a huge list of other measures. Although not detailed, younger patients responded better in the Stars study − enrolment included those aged 13-49. Neptune has enrolled patients 4-12 years old.

Other therapies in development for Angelman include Roche’s RG6091, which recently started phase I, and Genetx/Ultragenyx’s GTX-102, on which phase I/II data are expected next year. Both are trying to target the underlying genetic cause of the disease.

The following table notes additional fourth-quarter events for the smallest companies and includes consensus forecasts from EvaluatePharma. Evaluate Vantage has separately assessed expected catalysts for larger drug makers, and biotech companies with a market cap over $1bn.