LIDDS’ NanoZolid-TLR9 agonist demonstrates strong and durable preclinical anti-tumoral effect

UPPSALA, SWEDEN – LIDDS AB (publ) announces that intratumoral injection of NZ-TLR9, NanoZolid (NZ) formulation of a Toll-Like Receptor 9 (TLR9), results in strong antitumoral efficacy combined with prominent antitumoral immune responses in mouse tumor models. NZ-TLR9 forms an intratumoral depot which releases the TLR9 agonist for least 6 weeks and thus minimizes the need for repeated injections. Furthermore, we have identified both intratumoral- and plasma biomarkers needed to measure the activity of NZ-TLR9 in clinical trials.

LIDDS has completed a preclinical data package using a TLR9 agonist formulated with NanoZolid®(NZ-TLR9) showing that a single NZ-TLR9 injection is reducing tumor growth and improves the survival of mice, with increase of intratumoral cytotoxic T- cells and activated dendritic cells. The TLR9 agonist is released during at least 6 weeks with equal in vivo efficacy which minimizes the need for repeated injections, which are needed when using standard formulated TLR9 agonists. In addition, the study also identified plasma biomarkers which are suitable to measure the biological activity of NZ-TLR9 in coming clinical trial.

-I’m really happy to see our convincing preclinical data package with NanoZolid formulated TLR9, especially the six weeks of controlled release with strong anti-tumor effect. The results indicate that NanoZolid technology®, with controlled and sustained drug release, can be used to treat deep lying cancer tumors. These tumors are not suitable to be treated with standard TLR9 due to the necessity of weekly injections. The planning for a Phase I study treating solid tumors with intratumoral NZ-TLR9 is ongoing and we plan to start the study towards the second half of 2021, commented Monica Wallter, CEO of LIDDS.

About TLRs and TLR9
Toll-like receptors (TLRs) are key targets in the search for new treatments against cancer. TLRs are expressed on various immune cells, including dendritic cells, and upon activation they initiate the body’s immune response. TLR9 activation leads to an immunologically active tumor environment with recruitment of the cytotoxic T cells which are necessary for an antitumor response in immunotherapy. Thus, TLR9 agonists can convert immunologically “cold” tumors to immunologically “hot” tumors. The most promising target cancers for the TLR9 project are head and neck cancer, prostate cancer, sarcomas and lymphomas. These malignancies are diagnosed in around 2 million patients each year. The market for TLR agonists is expected to be worth hundreds of millions of dollars over the coming years.  

For additional information, please contact:
Monica Wallter, CEO LIDDS, +46 (0)737 07 09 22, [email protected]

This information is such that LIDDS AB (publ) is obliged to disclose pursuant to the EU Market Abuse Regulation. The information was released for public disclosure, through the agency of the contact persons above on October 26, 2020 at 08:30 CET.

LIDDS AB (publ) is a Swedish-based pharmaceutical company with a unique drug delivery technology NanoZolid®. NanoZolid® is a clinically validated drug development technology and superior in its ability to provide a controlled and sustained release of active drug substances for up to six months. LIDDS has licensing agreements where NanoZolid

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Stellarex Paclitaxel Coated Balloon Safe, Durable in PAD

A long-term real-world experience with Stellarex (Philips) drug-coated balloons (DCB) in the periphery strengthens the mass of recent evidence largely acquitting it and other paclitaxel-coated devices of any special mortality hazard.

A 4-year analysis based on the ILLUMENATE Global postmarket registry suggested that the DCB was safe and effective in a broad population of patients with often complex femoropopliteal lesions, fewer than one-third of whom required stents on a provisional basis.

Their target-limb amputation rate was only 0.8% and all-cause mortality was 8.1%, “very low for a cardiovascular patient group with claudication,” said Andrew Holden, MB, ChB, Auckland City Hospital, New Zealand, reporting the results during TCT Connect, the virtual edition of Transcatheter Cardiovascular Therapeutics (TCT) 2020.

The findings were consistent across prospectively defined subgroups by sex, diabetes, and target-lesion length, as well as the broader ILLUMENATE trial experience encompassing more than 2000 patients, he said.

And they impressed observers at TCT Connect, who called for an end to any stigma against paclitaxel-coated devices in peripheral vascular disease (PAD) and for tighter focus on randomized trials to refine their selection and targeted use.

As chronicled at length by theheart.org | Medscape Cardiology, a controversial meta-analysis published in December 2018 upended clinical trials looking at paclitaxel-coated devices for PAD revascularization by tying them to an almost 70% jump in relative risk (RR) for mortality at 2 years and a 93% RR increase at 5 years.

The findings led to a warning letter regarding the alleged risk from the US Food and Drug Administration (FDA), followed by a comprehensive public analysis by the agency and its independent advisors in June 2019, which acknowledged the existence of a safety signal.

Four months later, the FDA approved two sizes of the Stellarex for de novo and restenotic lesions in the superficial femoral and popliteal arteries. They joined other Stellarex DCBs and paclitaxel-coated peripheral devices already on the market, all of which account for the safety signal in their labeling.

“The mortality at 4 years is strikingly low. Normally, in a population like this, we would expect it to be at least 10% to 20% at 4 years,” Peter A. Schneider, MD, University of California, San Francisco, said as an observer of ILLUMENATE-Global at a media briefing.

“So, far from a doubling of mortality risk with paclitaxel, actually this appears to be less than what we would expect for a population like this.”

At the same press conference, Robert Lookstein, MD, MHCDL, said the findings represent “just really spectacular data in a real world subset — high degrees of severe calcification, high preponderance of diabetics. I think this just further reinforces the broad consensus among vascular specialists that DCB has really become the go-to therapy for patients with lifestyle-limiting claudication.”

ILLUMENATE-Global “is just another valuable contribution to the literature suggesting that this Stellarex balloon is a safe and effective technology in a real-world population,” said Lookstein, Ichan School of Medicine at Mount Sinai, New York City.

“I think right now, many of us are

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