Continued from page 18

17 Lakhani, NJ, LoRusso, P, Hafez, N et al. A phase 1 study of ALX148, a CD47 blocker, alone and in combination with established anticancer antibodies in patients with advanced malignancy and non- Hodgkin lymphoma. J Clin Oncol 2018; 36: 3068-3068. 18 Epidemiology in B-Cell Malignancies. Targeted Oncology. Jul 9, 2014. publications/special- reports/2014/hematologic- malignancies- issue1/epidemiology-in-b-cell- malignancies. 19Tarella, C et al. Rate of Primary Refractory Disease in B and T-Cell Non-Hodgkin’s Lymphoma: Correlation with Long-Term Survival. PLoS One. 2014; 9(9): e106745. 20Tang, Jun et al. The clinical trial landscape for PD1/PDL1 immune checkpoint inhibitors. Nature Reviews Drug Discovery. 2018; 17: 854-855. s/nrd.2018.210?WT.feed_name =subjects_drug-development.

innate and adaptive immunotherapies are immense and have the potential not only to expand the range of patients who can benefit from immunotherapy, but also to distinguish immunotherapy pharmaceu- tical companies from the rest of the competition. The impact these combination therapies can

have for patients is considerable. For instance, a Phase Ib/II study treated 22 patients with refracto- ry B-cell NHL (previously treated with a median of four lines of therapy) with 5F9 and rituximab. Of these patients, 50% had an objective response and 36% had a complete response. Of seven indolent follicular lymphoma (FL) patients, 71% had an objective response, while 45% had a complete response7. And objective responses were observed in 40% aggressive diffuse large B-cell lymphoma (DLBCL) patients with 35% having complete responses. That is nearly double the objective response and

more than four times the complete response for standard-of-care treatment for DLBCL in a large 2017 study8, and betters a 2014 study of idelalisib for relapsed indolent lymphoma by about 40% for objective response and a whopping seven times for complete response9. Considering that about 70,000 new cases of B-

cell NHL are diagnosed annually in the US, it has been estimated that there are approximately 11,500 DLBCL and FL patients that have received three or more previous treatments and are in grave need of new therapies18,19. At an average annual cost of $150,000 for an effective immunotherapy, such as a PD-1 or PD-L1 inhibitor, that translates to a revenue potential of nearly $1.8 billion for a salvage therapy in DLBCL and FL alone. It might be well worth the effort. And that is not

even considering all the other indications a com- bined innate-immune therapy might generate. Using this approach could be applied to preclinical evidence in infectious diseases, cardiovascular dis- eases and fibrotic diseases. In addition, companies can further differentiate

themselves from competitors in the market by adding a combination therapy approach to their portfolios. Indeed, a future where we could significantly

increase the chances of a complete response in patients across indications could considerably boost the value of combined innate-adaptive ther- apies. In fact, the chances of a complete response could increase so much that restoring the one-two punch of the innate and adaptive immune systems could become the standard of care for new cancer therapies, which raises the question: Can you afford NOT to include innate immune-boosting


therapies as part of your oncology development programme? A recent Nature publication indi- cates that in September 2018, there were 2,250 clinical trials on-going with T-cell checkpoint inhibitors20. Is it time to deploy those resources more broadly?


Dr Mark Chao, Co-founder of Forty Seven and Vice-President of Clinical Development, plays a leading role in the management of the company’s clinical trials and clinical development strategy. Mark completed his MD, PhD in cancer biology and hematology fellowship at Stanford University.

Dr Ranjana H. Advani, Saul Rosenberg Professor of Lymphoma and Physician Leader of the Lymphoma Clinical Care Program at Stanford University, specialises in research and treatment of Hodgkin and non-Hodgkin. She completed her medical education at Bombay University in India and residency and fellowship at Stanford.

Dr Jens Peter Volkmer, Co-founder of Forty Seven and Vice-President of Research and Early Development, oversees the company’s research to support ongoing clinical trials and leads the devel- opment of new therapeutic programmes. Jens received his medical degree from the Heinrich- Heine University in Duesseldorf, Germany.

Drug Discovery World Spring 2019

Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64