Clinical stage immuno-oncology company SOTIO Biotech and LegoChem Biosciences (LCB), a biotechnology company focused on developing its clinical-stage platform technology to develop antibody-drug conjugates (ADCs), have signed an exclusive collaborating and licensing agreement for five new ADC programs.

The agreement enables SOTIO to combine its proprietary antibodies with LCB’s ADC technology platform in order to deliver novel therapeutics for the treatment of solid tumors and includes LCB’s proprietary conjugation technology ConjuAll™, a next-generation ADC platform technology utilizing novel linker chemistry combined with site-specific enzymatic conjugation and potent linker-payload platform including multiple different payloads.

Radek Špíšek, MD., Ph.D, joined SOTIO in 2010. He has been a member of the company’s management team responsible for overseeing research and manufacturing. He was appointed Global CEO in March 2018.
Radek Špíšek, MD., Ph.D, joined SOTIO in 2010. He has been a member of the company’s management team responsible for overseeing research and manufacturing. He was appointed Global CEO in March 2018.

Under the terms of the multi-target agreement, LCB is eligible to receive upfront and potential milestone payments worth up to $1,027.5 million, payable based on certain developments and regulatory achievements, plus royalties on net sales. The deal includes upfront and near-term milestones worth up to $29.5 million, subject to the exercise of options and achievement of success-based milestones. No further financial details are disclosed.

“At SOTIO we are building an innovative pipeline of ADC programs and plan IND filing for our lead program SOT102 by the end of 2021.  The licensing agreement with our new, experienced partner LegoChem allows us to broaden our oncology pipeline with additional programs and solid tumor targets. We are looking forward to using the potential of LegoChem’s ADC technology platform and to develop innovative ADCs for patients in need,” explained Radek Špíšek, M.D., Ph.D., Chief Executive Officer of SOTIO.

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SOTIO will be responsible for research, development, manufacturing and commercialization of the ADC products, while LCB will support and work closely with SOTIO for the research activities and the manufacturing of components that are specifically related to its proprietary ConjuAll™ and the linker-payload technologies.

“This collaboration is yet another example that illustrates how the value proposition of the LCB platform can increase the competitive position of our partners within the ADC space. SOTIO is an ideal partner for LCB due to its expertise and strategic focus on innovative antibody-drug conjugates, and we look forward to working closely together on multiple innovative programs,” Yong-Zu Kim, Ph.D., Chief Executive Officer and President of LegoChem Biosciences.

The agreement with LegoChem Biosciences is in addition to the current development partnership between SOTIO Biotech and NBE-Therapeutics. Together with NBE Therapeutics SOTIO is developing ADCs based on NBE’s proprietary site-specific sortase-mediated antibody coupling (SMAC) conjugation platform. The ADCs utilize an anthracycline toxin called PNU, a highly potent cytotoxic agent, that leads to immunogenic cell death and elicits a long-lasting immune response.

Earlier this year, during the annual meeting of the 2021 American Association of Cancer Research (AACR) SOTIO presented early results of SOT102 (previously known as  SO-N102), a CLDN18.2 targeting antibody-drug conjugate based on a proprietary, highly specific monoclonal antibody conjugated to a potent cytotoxic drug molecule and is being developed in collaboration with NBE-Therapeutics.

In developing SOT-102, SOTIO leverages a highly potent anthracycline-based DNA-intercalating toxin, a highly potent metabolite of nemorubicin (MMDX), which is related to doxorubicin and termed PNU-159682.[1]

The active drug, PNU-159682, is up to 3-5000 times more potent on selected cancer cell lines than the standard doxorubicin (Adriamycin®, Rubex®).

Used as a payload in an antibody-drug conjugate, ultra-potent toxins like PNU-159682 require highly stable linkers that covalently attach the toxin to the antibody. To safely use this payload, a well-defined conjugation site with uniform stability is a crucial requirement.

The company has efficiently coupled this payload, modified via a stable amide and peptide bond linker, to the C-termini of antibody heavy and light chains using the company’s SMAC-Technology™. The novel ADCs have shown unprecedented preclinical data in efficacy, as well as safety, in multiple pipeline programs.

Complete responses were observed in all models, independent of CLDN18.2 expression levels, ranging from low (IHC1+) to high (IHC3+), with minimum efficacious doses between 0.2 mg/kg and 0.6 mg/kg. An acceptable tolerability profile was observed in preliminary toxicity studies at 10 mg/kg (mouse), 6 mg/kg (rat), and 1 mg/kg (cynomolgus monkey). SO-N102 demonstrated favorable pharmacokinetic properties with half-lives in the range of 8 days and 13 days in cynomolgus monkey and rat, respectively. The stability of SO-N102 without any significant loss of the payload was demonstrated in vitro and in animals.[1]

“The results from our preclinical proof-of-concept study of SOT102 not only demonstrate excellent signs of safety, tolerability, and efficacy in vivo, but also molecular stability and a greatly expanded therapeutic window. These findings provide SOTIO strong rationale for proceeding with in-human studies, which we look forward to initiating in early 2022,” Špíšek said.

IND-enabling studies of SOT102 are currently ongoing with an IND filing planned for the fourth quarter of 2021, followed by a first-in-human clinical study in patients with gastric and pancreatic cancer planned for the first half of 2022.

[1] Sadilkova LK, Valentova I, Hoskova S, Vopalensky P,  Bammert L Beerli R, Moebius U, Spisek R. Sadilkopva LK, Valentova I, Hoskova S, Vopalensky P. SOT102, a novel CLDN18.2-targeting antibody-drug conjugate with strong therapeutic potential in solid tumors expressing low target levels. Poster 1204. Presented during the 2021 annual meeting of the American Association of Cancer Research (AACR), held April 10 – 15, 2021 /May 17-21, 2021.

Featured Image: SOTIO Biotech Laboratory. Courtesy: © 2010 – 2021. SOTIO Used with permission.

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