ASCO 2019 Roundup

14th June 2019

The American Society of Clinical Oncology (ASCO) annual meeting in Chicago provides clinicians and drug developers an annual opportunity to share emerging clinical data and has long been seen as the place for unveiling the clinical results from the hottest drug development programmes. Many commentators have remarked that this year’s conference had fewer high-profile trial readouts compared with previous years. This is partly because drug developers are increasingly releasing exciting clinical data at other oncology conferences such as the American Association for Cancer Research (AACR) and European Society for Medical Oncology (ESMO) in a bid to release data as soon as possible.

This is also driving a shift to companies releasing data earlier in a drug programmes, with an increasing number of abstracts releasing early Phase 1 data compared with other years. It is also worth noting that recent ASCO meetings have set the bar very high for headline-grabbing announcements and results.

Key Abstracts from ASCO 2019:

It is a challenging task to select from the nearly 5,000 abstracts published at ASCO 2019, however highlighted below are some of the key readouts and themes coming out of this year’s meeting.

  • Checkpoint inhibitors – Merck’s PD-1 inhibitor (Keytruda / pembrolizumab) has demonstrated substantial improvement in 5-year survival in non-small cell lung cancer patients - here
  • Cell therapy - Adoptive T cell therapy (Iovance’s lifileucel) appears to be effective in cervical cancer driving complete responses in a subset of patients and evidence of durability - here
  • Ongogene-targeting – Amgen’s small molecule inhibitor of KRAS G12C (AMG-510), an “undruggable” oncogene found in a subset of lung cancer patients, has led to responses in half of patients treated, giving hope that KRAS may be a tractable target - here
  • Bispecific antibodies – Bispecifics continue to gain momentum in both haematological and solid cancers. For example the high dose of Amgen’s BCMA-targeted bispecific T cell engager (BiTE – AMG-420) continuing to show responses in relapsed / refractory multiple myeloma potentially competitive with engineered T cell therapy approaches - here
  • DNA Damage Response (DDR) – AstraZeneca and Merck’s PARP inhibitor (Lynparza / olaparib) continues to show promise in BRCA-mutated cancers, with emerging data showing increased progression free survival in BRCA-mutated pancreatic cancer patients - here

Of these, the surging interest and momentum in data generation in Bispecific antibodies and DNA Damage Response are particularly relevant for Arix and its portfolio companies.

Bispecific antibodies

The growing momentum behind bispecific antibodies as a modality and the impressive emerging data in both haematological cancers and solid tumours, has fuelled debate as to whether they could overtake engineered T cell therapies (such as CAR-T) as the optimal treatment, due to preferable manufacturing and delivery considerations. Harpoon Therapeutics (Harpoon), an Arix portfolio company, is developing next generation multispecific antibodies, called TriTACs, for a number of haematological and solid cancers. The company was co-founded by the ex-Chief Scientific Officer of Micromet, the company that developed the first FDA approved bispecific antibody (Amgen’s Blincyto), who is well placed to engineer the next generation of these drugs. Mark Chin, Investment Director at Arix, is on Harpoon’s board and works closely with the company.

Harpoon’s technology is differentiated from traditional bispecifics by the inclusion of a half-life extending albumin-binding arm which improves dosing schedule and by the small size of the drug (about 3x smaller than bispecific antibodies), which improves TriTAC penetration into solid tumours. Emerging data was presented at ASCO 2019 with bispecifics targeting BCMA in relapsed / refractory multiple myeloma (here), and PSMA in prostate cancer (here), validate the potential for Harpoon’s HPN217 and HPN424 and we are optimistic that the advantages of the TriTAC technology should position these well for Best-in-Class status.

DNA Damage Response

There is growing excitement about the potential of drugs targeting the DNA Damage Response (DDR) in cancer, driven primarily by the steady stream of impressive clinical data generated by the PARP inhibitors, especially AstraZeneca and Merck’s Lynparza (olaparib). Data at ASCO 2019 has shown that Lynparza also has a positive effect on the progression free survival of pancreatic cancer patients with mutated BRCA (here), which is encouraging given the notoriously poor prognosis of this patient population. The positive data flowing from PARP inhibitors has ignited excitement in the drug development world about the potential for DDR targeted therapies.

In 2016, when excitement in oncology was almost exclusively reserved for immunotherapy, the investment team at Arix spotted an opportunity to invest in a high quality DDR-focused company, Artios Pharma, before market sentiment for DDR had picked up. Finding and drugging new targets in the DDR space is extremely challenging, and a major attraction of Artios was that its CEO and CSO were instrumental in the invention and development of Lynparza, and therefore well placed to lead the discovery efforts on the next generation of DDR targeted therapies. Artios has since raised $120 million and is moving towards the clinic with a number of exciting DDR targeted drugs, led by its Polymerase θ inhibitor, which could be helpful in an even wider range of patients than Lynparza.

Global Oncology Trends

Oncology remains a high area of interest and research. A record number of new oncology drugs have been approved in recent years, bringing new treatment options to patients. Over the past five years, 57 newly launched oncology therapeutics received approval for 89 indications, with some drugs treating multiple tumour types. In 2018, a record 15 new oncology therapeutic drugs were launched for 17 indications.

Spending on all medicines used in the treatment of patients with cancer worldwide reached nearly $150 billion in 2018 up 12.9 percent for the year and marking the fifth consecutive year of double-digit growth.

Through 2023, compound annual growth in oncology therapeutics spending is expected to be 11–14 percent bringing total estimated spending to $200–230 billion worldwide; $220–250 billion when supportive care is included within the estimate[1].

[1]IQVIATMGlobal Oncology Trends 2019: Therapeutics, Clinical Development and Health System Implications