BIOLOGICS
in a parallel manner within several hours combined with the linear scalability of the system allows fast scale-up for use in clinical studies and may save up to one year compared to conventional cell-based (CHO) expresson systems. Importantly, the identification of a cost-effective energy source – by generating nucleotide triphosphates via the Krebs cycle and oxidative phosphorylation incorporated into the extract – allows the in vitro expression of large amounts of proteins in a cost-effective manner.
ADCs and bispecific antibodies: promising new therapies “Antibody-drug conjugates, as a new class of targeted therapies, hold much promise, especially in oncology,” says William Newell, CEO of Sutro. “Technology platforms for the development of next-generation ADCs should provide control over the number and placement of the drugs conjugated to the highly targeted antibody. The current state of the art results in mixtures of multiple species of ADCs, and this gives sub-optimal PK, stability and efficacy. In addition, therapeutics should only be active in the targeted, diseased cells. Therefore the development of effective ADCs is very complex and takes time. Many parameters have to be finely tuned, and many variants have to be tested. In fact, this can take years. Our technology enables the production of many variations of antibodies, using non-natural amino acids for site-specific attachment in multiple different sites, in five to 10 hours, which then permits the rapid conjugation of multiple different linkers and multiple different warheads.”
Once the best molecule has been identified, Sutro’s cell-free extract enables the same process to be scaled linearly for rapid clinical- trial-scale production and therefore the technology can be used to rapidly optimise and develop homogeneous ADC therapeutics. Within about two months, it is now feasible to systematically and rapidly evaluate all possible sites within an IgG (immunoglobulin G) for many properties including drug conjugation efficiency, binding affinity, PK, , stability and aggregation propensity. It is also possible to test libraries of linker-warheads and produce single-species product candidates optimised for tumour cell killing. Once the optimum sites have been identified, the candidates can be taken into animal efficacy studies. Other areas Sutro is currently exploring include bispecific antibodies, which is the fusion of two antibodies or antibody
30 sp2 Inter-Active March/April 2012
fragments: “Single-chain variable fragments as recombinant antibody fragments are attractive building blocks for the assembly of bispecific antibodies, but they are hard to express, have limited half-lives, poor stability and low affinity,” says Newell. “Our biochemical protein synthesis technology platform has advantages that can overcome these hurdles, and also enables development of novel scaffolds with superior manufacturability profiles.”
Sutro has started upgrading its facilities with a new cGMP clinical materials plant which will be fully completed and operational later this year. The plant will operate the company’s cell-free production processes and incorporate two clean rooms: one for the production of the E. coli extract and the other for completely cell-free protein synthesis and purification. Sutro’s facilities are currently outfitted to achieve production volumes that would be adequate to meet the needs for Phase 1 and early Phase 2 trials, ie non- cGMP materials.
Partnership opportunities As well as developing its ADCs and bispecific antigen-binding molecules for targeted cancer therapy, Sutro is pursuing two types of partnership opportunities: first, collaborations with pharma and biotech companies that want to develop next-generation ADCs and bispecific antibodies; and second, as in its partnership with Pfizer, partnerships with companies that are interested in exploring inaccessible proteins as therapeutics. In these types of relationships, Sutro works in collaboration with research groups to discover and optimise proteins that these companies have not been able to express with conventional expression systems for therapeutic research purposes. “Our near-term objective is to put in place a couple of collaborations around the discovery and development of novel tumor-targeted cancer therapeutics, whether ADCs or bispecific antibodies,” says Newell. “We have the capability of producing high-fidelity, single- species ADCs, in which the conjugation position has been optimised for enhanced PK and tumour cell killing. We are committed to producing ADCs that have better therapeutic indices and better payload internalisation than the current state of the art. We also offer the opportunity to quickly compare different classes of warheads with different mechanisms for killing. “We are also working aggressively on bispecific and multispecific antibodies with an eye towards conjugating them as well. The goals would be to offer attractive therapeutics that can attack multiple different tumour types
Meet William Newell of Sutro Biopharma
William Newell has more than ten years of senior management experience in the biotechnology industry. He joined Sutro Biopharma as CEO in January 2009, having previously served as President of Aerovance, Inc, a venture-backed company developing clinical assets for respiratory diseases. He was also previously Chief Business Officer and Senior Vice President at QLT, Inc and served in several senior management positions at Axys Pharmaceuticals, Inc, where he ultimately served as Senior Vice President, Corporate and Business Development prior to the acquisition of the company by Celera Genomics. For the 15 years prior to joining Axys,he practised law at Bingham McCutchen LLP.
or to enhance tumour cell killing by shutting down resistance mechanisms.
“Biopharmaceuticals will continue to grow and be the dominant force in terms of market growth in health care and next-generation ADCs especially will be a focus for pharma and biotech companies. The creation and advancement of new technology platforms will allow for the rapid, methodical and systematic study of new ADCs and other biologics drug candidates. Additionally, the first set of ADCs targets cancer, but the ADC technology hold promises for other diseases as well, and our technology has the potential to exploit these exciting new opportunities of the future,” he concludes.
Further information William Newell Chief Executive Officer Sutro Biopharma, Inc 310 Utah Ave, Suite 150 South San Francisco, CA 94080 USA Tel: +1 650 392 8412 Fax: +1 650 872 8924 Email:
general@sutrobio.com Web:
www.sutrobio.com
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