Tubulis Doses First Patient in Phase I/IIa Trial Investigating ADC Candidate TUB-040 in Ovarian Cancer and Lung Adenocarcinoma
June 20 2024 - 5:00AM
Business Wire
- TUB-040 is a next-generation NaPi2b-targeting Exatecan ADC
based on Tubulis’ proprietary P5 technology with superior
biophysical properties that demonstrated effective and durable
responses in a range of preclinical models
- The clinical trial will enroll up to 140 patients with
platinum-resistant high-grade ovarian cancer or relapsed/refractory
adenocarcinoma non-small cell lung cancer in the US, the UK and
Europe
Tubulis announced today that the first patient has been treated
in its first Phase I/IIa trial (NAPISTAR 1-01, NCT06303505). The
study is evaluating Tubulis’ next-generation antibody-drug
conjugate (ADC) TUB-040 in patients with platinum-resistant
high-grade ovarian cancer (PROC) or relapsed/refractory
adenocarcinoma non-small cell lung cancer (NSCLC), who have
exhausted other available treatment options. TUB-040 targets
NaPi2b, a highly overexpressed antigen in ovarian cancer and lung
adenocarcinoma. The candidate is the first to enter the clinic from
the company’s growing pipeline and represents one of Tubulis’ two
lead candidates developed using its proprietary suite of platform
technologies, which enable the creation of uniquely matched ADCs
with superior biophysical properties.
The multicenter, first-in-human, dose escalation and
optimization Phase I/IIa study aims to investigate the safety,
tolerability, pharmacokinetics, and efficacy of TUB-040 as a
monotherapy. The trial will be conducted in the US as well as the
UK, Spain, Belgium, and Germany. Phase Ia comprises the dose
escalation and will determine safety and the maximum tolerated dose
or the identified dose for optimization, whereas Phase IIa will
focus on dose optimization, safety, and preliminary efficacy of
TUB-040. The first patient has been dosed in the US following IND
approval by the FDA.
“ADCs are beginning to show their potential as a core treatment
modality replacing conventional chemotherapy for several solid
tumor indications. Based on our preclinical data we are convinced
that TUB-040 can represent a new option for the effective treatment
of NSCLC and ovarian cancer patients,” said Günter Fingerle-Rowson,
MD, PhD, Chief Medical Officer at Tubulis. “The novel P5 technology
we use in TUB-040 improves upon current limitations due to
off-target toxicity and restricted durability, the main challenges
of current ADC treatments. By achieving reduced non-target toxicity
together with a more specific, more powerful, and continued
on-tumor delivery of the payload, we aim to improve long-term
anti-tumor responses and, ultimately, clinical outcomes for
patients.”
“Initiating our first clinical trial represents an important
milestone for the entire Tubulis team and underscores our vision to
innovate on all fronts of the ADC design for patient benefit,” said
Dominik Schumacher, PhD, Chief Executive Officer and Co-founder of
Tubulis. “Our objective is to achieve clinical proof-of-concept for
our lead candidate, TUB-040, and validate our differentiated
platform approach to ADC development.”
TUB-040 consists of a humanized, target-specific, Fc-silenced
IgG1 antibody equipped with Tubulis’ proprietary Tubutecan
linker-payload technology, which is based on P5 conjugation
chemistry and the topoisomerase-1 inhibitor Exatecan. Tubulis
recently presented a comprehensive preclinical data set at AACR,
demonstrating the superior stability and minimal loss of
linker-payload conjugation for their lead candidate. In a range of
preclinical models, Tubulis was also able to show high and
long-lasting anti-tumor responses, even at lower expression levels
of NaPi2b, with an excellent safety and tolerability profile.
About TUB-040 and the P5 Technology
Tubulis’ lead antibody-drug conjugate (ADC) TUB-040 is directed
against Napi2b, an antigen highly overexpressed in ovarian cancer
and lung adenocarcinoma. It consists of an IgG1 antibody targeting
Napi2b connected to the Topoisomerase I inhibitor Exatecan through
a cleavable linker system based on the company’s proprietary P5
conjugation technology with a homogeneous DAR of 8. P5 conjugation
is a novel chemistry for cysteine-selective conjugation that
enables ADC generation with unprecedented linker stability and
biophysical properties. It originated from the fundamental work of
Prof. Christian Hackenberger at the Leibniz-Forschungsinstitut für
Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP),
which unlocked the use of phosphorus chemistry for superior
bioconjugation. Preclinical pharmacokinetic analysis also
demonstrated that TUB-040 efficiently delivers its payload to the
tumor while reducing off-site toxicities. The candidate is
currently being investigated in a multicenter Phase I/IIa study
(NAPISTAR 1-01, NCT06303505) that aims to evaluate the safety,
tolerability, pharmacokinetics, and efficacy of TUB-040 as a
monotherapy.
About Tubulis
Tubulis’ suite of proprietary platform technologies generates
uniquely matched antibody-drug conjugates with superior biophysical
properties for treating solid tumors. By demonstrating durable
on-tumor delivery of the payload and long-lasting anti-tumor
activity, we have reached the clinic with our first program,
TUB-040, in ovarian and non-small cell lung cancer. The second
candidate from our growing pipeline, TUB-030, is set to follow in
the near-term. We will solidify our leadership position by
continuing to innovate on all aspects of ADC design to expand their
therapeutic potential for our pipeline, our partners and for
patients. Visit www.tubulis.com or follow us on LinkedIn.
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For Tubulis Dominik Schumacher, CEO & Co-Founder
Phone: +49 175 800 5594 Email: contact@tubulis.com
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Stephanie May, PhD Phone: +49 (0) 171 185 56 82 Email:
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