Sweden-based Simris Group, a European biologics company focused on extracting high value biological active compounds from microalgae and cyanobacteria, has signed a strategic collaboration agreement with Lonza.  The agreement aims to help the Simris Group to commercialize the company’s antibody-drug conjugates (ADC) payload platform technology.

Julian Read, Chief Executive Officer of the Simris Group

With more than 210 novel ADC clinical trials started in 2022, the market for novel ADC continues to develop in line with their recognition as effective, stable and reliable anti-cancer therapeutics.

Novel payloads with novel modes of action, such as those developed by Simris Biologics, the German subsidiary of Simris Group previously known as Cyano Biotech, show great promise as effective cancer therapeutics that could improve quality of life for many cancer patients.

Simris Biologics holds a library of more than 1,200 strains of cyanobacteria.  In addition, the company has identified more than 5,000 novel, natural compounds from cyanobacteria in this library, each with a variety of applications.

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Some of these compounds are showing promising anti-cancer activity. Based upon the company’s patent protected platform Simris is developing these compounds for the next generation of safer ADC payloads with a high therapeutic index.

The company’s first payload class includes microcystins. These payloads are heptapeptide toxins comprising more than 300 natural analogues. The toxic mode of action of these microcystins is based upon the inhibition of two protein phosphatases, with picomolar IC50 values, are involved in homeostasis of cells. The inhibition of these protein phosphatases leads to the interruption of essential signal transductions and to the collapse of the cytoskeleton, causing apoptosis.

As part of an ADC, which is composed of an antibody tethered to a cytotoxic small-molecule drug payload through a chemical linker, these highly cytotoxic molecules microcystin variants, modified by Simris as part of the company’s proprietary payload technology platform, are directly delivered to cancer cells and are generally considered non-toxic within the systemic circulation.  Coupled to target-specific antibodies the resulting ADC is internalized in the cancer cell, kills cancer cells while saving normal, healthy, tissues.

However, despite the relatively simple concept, various parameters must be considered when designing optimal ADCs. This includes the development of highly potent cytotoxic agents which can be used as payload. [1] Over the last decade, a better understanding of the biology of cancer coupled with innovations in the identification of potentially new payloads, have resulted in the development of payloads that are overcoming drug resistance mechanisms, showing efficacy against slow growing tumors, and enabling the use of biomarkers to better understand ADC PK/PD relationships. [2]

The structural diversity of naturally occurring microcystins offers excellent safety profiles for the treatment of both hematological and solid malignancies.

Although more than 12 ADCs have demonstrated sufficient efficacy and safety to warrant US Food and Drug Administration (FDA-) approval, in clinical use ADCs have shown  substantial toxicity in patients being treated. Furthermore, a large number of ADCs have failed in clinical development due unacceptable dose-limiting toxicities (DLTs).

With a relatively small group of available payloads, including monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), the maytansine derivatives DM1 and DM4, calicheamicin, SN38 (an active metabolite of the Topoisomerase I inhibitor Irinotecan), Dxd (and exatecan derivative), and pyrrolobenzodiazepine (PBD) used in the majority of approved ADCs and ADCs under development, there is a need for additional payload classes.

In vitro studies with microcystin-based ADCs have shown efficacies in picomolar ranges (e.g. 32 pM) against several cancer cell lines, leading to the conclusion that these novel cytotoxic compounds my be among the next payload family to enter clinical trials.

Beyond microcystins
In addition to microcystins, Simris is developing 15 other known cyanobacterial non-ribosomal peptide payloads classes, including cyptophycins, largarzole, apratoxin and aurilides, all of which are suitable for ADC payload development. Like the microcystins, these novel toxins can also be further developed as novel ADC payloads. The company’s natural product library includes more than 300 compounds showing cytotoxic tissue specific-activity. Each of these compounds has the potential to be used as future ADC payloads.

Agreement
Under the terms of the agreement, Lonza will integrate Simris’ ADC payload technology into the Lonza Bioconjugation Toolbox and will gain the exclusive right to offer the technology to new and existing customers seeking novel payloads to develop into novel antibody-drug conjugates (ADCs).

Bioconjugation Toolbox
The Lonza Bioconjugation Toolbox comprises a range of tailored solutions for the technology selection, development, and manufacturing of bioconjugates to advance the development of novel bioconjugate-based therapies.

In return, Simris will promote Lonza to customers as its exclusive contract development and manufacturing organization (CDMO) partner for services using its ADC technology.

“We are delighted that Lonza shares our confidence in the potential of our ADC payload technology,” said Julian Read, Chief Executive Officer of the Simris Group.

“This strategic partnership will help Simris to reach new customers and Lonza’s market-leading capabilities as a CDMO increase the likelihood that our payloads will reach clinical use and thereby improve life quality for those unfortunate enough to suffer from cancer,” Read added.

Access to novel payloads
 “This new collaboration with Simris allows us to offer customers exclusive access to novel payloads derived from cyanobacterial natural products, as part of the Lonza Bioconjugation Toolbox,” noted Iwan Bertholjotti, Senior Director Commercial Development, Bioconjugates, Lonza.

“Our partnership with Simris enables us to advance the development of novel bioconjugates with the potential to transform cancer therapy and patient outcomes,” Bertholjotti concluded.

Reference
[1] Perez HL, Cardarelli PM, Deshpande S, Gangwar S, Schroeder GM, Vite GD, Borzilleri RM. Antibody-drug conjugates: current status and future directions. Drug Discov Today. 2014 Jul;19(7):869-81. doi: 10.1016/j.drudis.2013.11.004. Epub 2013 Nov 15. PMID: 24239727.
[2] Tumey, L.N. (2018). Next Generation Payloads for ADCs. In: Damelin, M. (eds) Innovations for Next-Generation Antibody-Drug Conjugates. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-78154-9_8

Featured image: Cultivation. Photo courtesy: © 2020 – 2023 Simris Biologics, the German subsidiary of Simris Group previously known as Cyano Biotech. Used with permission.

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