Special Report on Stem Cells (DDNews)

September 10, 2020

“Conventional therapy tends to reduce tumor burden and improves symptoms but may fail to eradicate tumor-initiating cells, leading to eventual recurrence and drug resistance,” they suggested. “Therapies targeting tumor-initiating cells may, therefore, work best alongside conventional therapies that debulk the tumor mass.”

Such debulking steps may be particularly important for solid tumors, adds Stern, as therapeutics like antibodies are quite large and can be limited in their capacity to reach the target cells. Initially shrinking the tumors using chemotherapy might facilitate immunotherapeutic access.

NeoTX Therapeutics and Active Biotech, meanwhile, are working on immunotherapy with naptumomab, which fuses the Fab fragment of an antibody targeting 5T4 with an engineered bacterial superantigen that activates T cell responses.

In preclinical studies, naptumomab has shown synergistic anti-tumor effects and has extended overall survival when combined with checkpoint inhibition.

At the 2018 AACR meeting, researchers tested naptumomab and an anti-PD-1 as monotherapy or in combination in low immunogenic mouse tumor models. Although naptumomab alone showed some capacity to activate T cells and increase tumor infiltration and the anti-PD-1 had no effect, the combination more dramatically increased serum cytokines and CD8:CD4 ratio in the tumors, resulting in reduced tumor burden and prolonged media survival.

Findings like these led to a Phase 1b/2 clinical trial, currently recruiting, that combines naptumomab with AstraZeneca’s anti-PD-1 durvalumab versus advanced and metastatic solid tumors. The first patient in this study was dosed last October.

“The dosing of the first patient in our Phase 1b trial is a significant milestone for NeoTX, as it is our first clinical-stage molecule developed with our Selective T Cell Redirection (STR) platform,” said company CEO Asher Nathan in announcing the milestone. “Previous clinical studies have shown Nap to be well tolerated, and preclinical work conducted by the NeoTX team supports its broad potential in treating advanced and metastatic tumors, especially in combination with checkpoint inhibitors.”

Credit: DDNews.com

Leveraging the Native Immune Response to Fight Cancer (Pharma’s Almanac)

July 1, 2020

Unlike checkpoint inhibitors and CAR-T cell therapies that activate the immune system artificially, selective T cell redirection technology from NeoTX activates immune cells away from the suppressive tumor environment, resulting in a powerful — yet safe — native antibacterial immune reaction.

Resurrecting a Drug with a Checkered Past

NeoTX Therapeutics is a clinical-stage immunotherapy company developing a novel technology initially licensed from Active Biotech in 2016. Naptumomab estafenatox (Nap) was being developed for the treatment of cancer by Active Biotech and had shown exciting positive results in a phase I study but failed to show sufficient efficacy in a phase II trial.

A closer examination of both studies suggested that Nap deserved further investigation. In phase I trials, a patient with non-small cell lung cancer (NSCLC) for whom three prior lines of therapy had failed was treated for six months with Nap. Even though he received no further treatments, this patient remained alive for 11 years and died of causes unrelated to cancer. The study also uncovered no concerning safety issues. 

The existing results led Active Biotech to move straight to a phase II/III study without any additional pilot trial. This follow-on study was, unfortunately, conducted in renal carcinoma, for which the standard of care at the time was interferon-α. We know today that interferon-α has significant negative interactions with Nap and that these interactions led to the failure of the trial.

Benefits of a Native Immune Response

Most immunotherapies on the market are designed to elicit some form of artificial immune response. Two difficulties in artificial manipulation include the vast complexity of the immune system and our lack of an in-depth understanding of how it functions. As a result, the generation of non-natural responses can often have many negative, unintended consequences. In addition, some therapies, such as bispecifics, aim to activate all T cells. This approach faces challenges, because T cells eventually become worn out after being activated. Thus, activating all T cells can ultimately deplete their supply.

Nap differs from current standard-of-care therapies because it relies on selective T cell redirection (STR) technology, which effectively converts a weak immune response against cancer to a powerful but specific, natural, antibacterial immune reaction. Nap is a recombinant fusion protein consisting of the antigen-binding fragment of a monoclonal antibody, directed towards the tumor-associated oncofetal trophoblast glycoprotein antigen 5T4, attached to a genetically engineered form of superantigen staphylococcal enterotoxin E (SEA/E-120).

Importantly, only T cells that express the superantigen receptor — approximately 1–2% of all T cells — are activated by Nap. These T cells undergo natural expansion and activation in the permissive environment of the periphery and lymph nodes. Once activated, they multiply rapidly and traffic to the tumor. Meanwhile, NAP binds to the tumor and acts as a neoantigen mimetic that the trafficking T cells can recognize, enabling them to kill the cancer.  The trafficking T cells can invade desert tumors and alter the tumor microenvironment, opening it up to further attack by other components of the immune system. 

Like the NSCLC cancer patient in Active Biotech’s phase I study who lived for an additional 11 years without any further treatment, we have seen that mice treated with Nap maintain the ability to fight off cancer after treatment is completed. Specifically, mice that exhibit a complete response when treated with NAP retain the ability to fight off other subsequent cancers, remaining cancer-free.

Nap, therefore, may provide a means for overcoming drug resistance, even for rapidly evolving cancers. STR technology appear to reboot the immune system, allowing it to evolve as cancers do. 

Synergy with Other Immunotherapies

In addition to breaking drug resistance by binding bacterial determinants to the tumor surface, STR technology carries the potential to augment the effectiveness of checkpoint inhibitors and other anticancer approaches. With such a powerful immune response generated by Nap, we believe that upregulation of checkpoints in the tumor microenvironment is likely to occur, thus enabling the enhanced performance of other cancer drugs, such as PD1/PDL1 inhibitors. 

In fact, we believe that STR technology will be synergistic with all of the major modalities for cancer treatment, including checkpoint inhibitors, which have revolutionized the field, and traditional chemotherapy, which is still widely used for cancers that don’t respond to checkpoint inhibitors.

Clinical Investigation in Progress 

Nap, NeoTX’s lead candidate and first STR platform drug, is currently in clinical development for advanced and metastatic solid tumor indications. Nap has significant potential as a monotherapy and in combination with chemotherapy, checkpoint inhibitors, and CAR-T technologies.

Previous clinical trials have found Nap to be well tolerated in hundreds of patients and demonstrated preliminary signals of efficacy. Preclinical work conducted by the NeoTX team supports its broad potential in treating advanced and metastatic tumors, especially in combination with checkpoint inhibitors.

A phase Ib clinical trial of Nap is ongoing in collaboration with AstraZeneca. The open-label, multicenter, dose-finding phase Ib study is currently enrolling. Patients are dosed with a combination of Nap and AstraZeneca’s checkpoint inhibitor IMFINZI® (durvalumab). NeoTX aims to establish the maximum tolerated dose before advancing to a larger cohort-expansion phase in the Unites States that will include indications known to respond well to checkpoint inhibitors, such as pancreatic and colon cancer.

Platform Technology

Because the superantigen is the same, regardless of the cancer being targeted, the STR approach is indeed a platform technology. The homing molecule can be designed to target many different types of tumor cells, allowing the development of a range of novel drug products. 

Due to its potential as a truly general solution for cancer treatment, STR technology is attracting significant attention. Once we gather more data from the ongoing clinical trials and are able to present hard and fast clinical evidence, we expect to see that interest materialize in the form of numerous partnerships for the investigation of combination treatments with Nap and other existing cancer therapies. 

Separately, NeoTX is actively exploring in-licensing deals and partnerships that could give the company access to new early-stage drugs that could be complementary to the STR platform. This activity will be funded in part by cash ($45 million) raised in a Series C financing round that closed in February 2020. To date, we have raised over $60 million, all from private investors. 

Our team at NeoTX includes both highly experienced scientists, such as Nobel Prize winner Prof. Roger Kornberg, and people with expertise in drug development and commercialization, such as the well-known drug developers Dr. Marcel Rozencweig and Dr. Robert Kramer. Early-stage clinical research is conducted in Israel and backed by highly experienced investigators interested in novel medications. Later-stage trials will be conducted in the United States and managed from our U.S. office. 

Going forward, our strategy for growth revolves around discovering, acquiring, and developing technologies that exploit novel mechanisms that enhance the immune system’s ability to attack tumors and developing business partnerships that leverage our STR platform technology. Because we want to stay focused on the development of novel therapies with real potential to impact patient lives, we intend to commercialize proprietary products through corporate alliances. 

Credit: Pharma’s Almanac.com

Neotx closes $45M C round for second coming of immuno-oncology agent (BioWorld)

February 21, 2020

DUBLIN – Neotx Therapeutics Ltd. raised $45 million in a series C round to continue clinical development of an immuno-oncology agent that already has a long clinical history behind it. Its lead molecule, naptumomab estafenatox, is a fusion protein comprising an antibody fragment that recognizes the oncofetal antigen 5T4 and a bacterial “super-antigen” comprising a modified version of the Staphylococcal enterotoxin A.

Credit: bioworld.com

NeoTX Closes $45 Million Series C Financing

February 19, 2020
REHOVOT, Israel

REHOVOT, Israel, Feb. 19, 2020 (GLOBE NEWSWIRE) — NeoTX Therapeutics, a clinical-stage biotechnology company leveraging its proprietary Selective T cell Redirection (STR) platform to develop targeted anticancer immunotherapies, has closed a $45 million Series C financing.  In conjunction with the financing, former vice chairman of The Blackstone Group, J. Tomilson Hill, Chairman of NDFOS Co., Ltd, Andrew Kim, Paul T. Marinelli and Nobel laureate Dr. Roger Kornberg, the chief scientific officer of NeoTX have joined the NeoTX Board of Directors. To date, NeoTX has raised over $60 million. NeoTX plans to use the Series C proceeds to advance its STR platform for the treatment of advanced and metastatic solid tumors as well as to in-license new technologies.

“With the funds raised in this financing, we intend to complete the dose escalation phase of the Phase 1b trial of naptumomab estafenatox (“Nap”) in combination with durvalumab  and continue to develop our patented STR platform,” said Asher Nathan, chief executive officer of NeoTX. “Our platform, which uniquely leverages the body’s natural antibacterial immune response to selectively redirect T cells to kill the tumor, has the potential to be applicable in a variety of solid tumor indications and in combination with other immunotherapies. We look forward to the clinical advancement of Nap and expanding our platform in order to provide new options to patients suffering from advanced cancers.”

The open-label, multicenter, dose-finding Phase 1b study of Nap (NCT03983954) is currently enrolling. Patients are dosed with a combination of Nap and AstraZeneca’s (NYSE: AZN) checkpoint inhibitor IMFINZI® (durvalumab). NeoTX aims to establish the maximum tolerated dose before advancing to a larger cohort expansion phase in the Unites States.

Israeli co NeoTX Therapeutics raises $45m (Globes)

February 19, 2020

The Rehovot-based company is leveraging its proprietary Selective T cell Redirection (STR) platform to develop targeted anticancer immunotherapies.

Israeli clinical-stage biotechnology company NeoTX Therapeutics has closed a $45 million Series C financing round. The Rehovot-based company is leveraging its proprietary Selective T cell Redirection (STR) platform to develop targeted anticancer immunotherapies.

To date, NeoTX has raised over $60 million. NeoTX plans to use the proceeds of the latest financing round to advance its STR platform for the treatment of advanced and metastatic solid tumors as well as to in-license new technologies.

NeoTX CEO Asher Nathan said, “With the funds raised in this financing, we intend to complete the dose escalation phase of the Phase 1b trial of naptumomab estafenatox (Nap) in combination with durvalumab and continue to develop our patented STR platform. Our platform, which uniquely leverages the body’s natural antibacterial immune response to selectively redirect T cells to kill the tumor, has the potential to be applicable in a variety of solid tumor indications and in combination with other immunotherapies. We look forward to the clinical advancement of Nap and expanding our platform in order to provide new options to patients suffering from advanced cancers.”

Credit: en.globes.co.il

NeoTX’s $45 million Series C to fund Phase I trial (The Pharma Letter)

February 19, 2020

Israeli company NeoTX, a biotech firm with a selective t-cell redirection (STR) platform for developing…

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Credit: thepharmaletter.com

NeoTX raises $45m for STR immunotherapy enhancing platform (Pharmaceutical Technology)

February 19, 2020

Israel-based NeoTX has closed its Series C financing round with $45m raised; this brings the company’s total funding to $60m.

NeoTX chief executive officer Asher Nathan said: “With the funds raised in this financing, we intend to complete the dose escalation phase of the Phase 1b trial of naptumomab estafenatox (Nap) in combination with durvalumab and continue to develop our patented STR [Selective T cell Redirection] platform.”

The company uses the STR platform to improve the response rate of current immunotherapies targeting solid tumours. Nathan explains: “Our platform, which uniquely leverages the body’s natural antibacterial immune response to selectively redirect T cells to kill the tumour, has the potential to be applicable in a variety of solid tumour indications and in combination with other immunotherapies.”

Nap is NeoTX’s lead programme and it directly targets tumours expressing the 5T4 antigen, which includes many advanced and metastatic solid tumours. NeoTX licensed the drug from Active Biotech in 2016, and began enrolling and dosing patients in its Phase 1b study in October 2019.

In this study, Nap is combined with AstraZeneca’s anti-programmed cell death-1 (PD1) checkpoint inhibitor Imfinzi (durvalumab); this follows the signing of a February 2019 collaboration between NeoTX and AstraZeneca. NeoTX also believes its drug has promise as a monotherapy in various solid tumours.

Nathan commented: “We’re looking forward to bringing this therapy to patients suffering from advanced cancers that have thus far been unresponsive to therapy with checkpoint inhibitors alone.”

The company also wants to use this $45m funding to in-license further technologies and products.

Credit: Pharmaceutical Technology

Israeli biotech NeoTX lands $45M series C for combo I-O cancer trials (Fierce Biotech)

February 19, 2020

NeoTX Therapeutics has nabbed a healthy $45 million third funding round as it looks to continue work on its early-stage cancer combo test and in-license new tech.

The Rehovot, Israel-based biotech is working on a Selective T cell Redirection (STR) platform for its oncology immunotherapies and now brings its total funding haul to $60 million.

NeoTX plans said in a brief update that it plans to use the series C proceeds to advance its STR platform “for the treatment of advanced and metastatic solid tumors as well as to in-license new technologies.”

Naptumomab estafenatox (aka Nap) is the lead compound in NeoTX’s STR platform and is designed to target the 5T4 antigen, which the biotech says is present on “many tumors.” The experimental drug was licensed from Active Biotech four years ago after it failed to help kidney cancer patients and was ditched by its original owner.

NeoTX is hoping it can brush off this flop and combine it with the right therapy to kick-start it into action. Part of the cash will be used for its ongoing, open-label phase 1 of Nap in combination with AstraZeneca’s checkpoint inhibitor Imfinzi (durvalumab) in solid tumors that have spread.

The trial started last year, and it “aims to establish the maximum tolerated dose in the dose-escalation Phase 1b study before advancing to a cohort expansion study.”

When first working on STR, Active Biotech said the platform in preclinical tests could boost the anti-tumor activity of checkpoint inhibitors (such as Imfinzi) and can “lead to long-lasting immunity against the tumor.” Studies will now try to prove this.

“With the funds raised in this financing, we intend to complete the dose escalation phase of the Phase 1b trial of Nap in combination with durvalumab and continue to develop our patented STR platform,” said Asher Nathan, CEO of NeoTX.

“Our platform, which uniquely leverages the body’s natural antibacterial immune response to selectively redirect T cells to kill the tumor, has the potential to be applicable in a variety of solid tumor indications and in combination with other immunotherapies. We look forward to the clinical advancement of Nap and expanding our platform in order to provide new options to patients suffering from advanced cancers.”

Credit: Fierce Biotech

After digging through discards, biotech startup is making a $45M bet it can fix a failed cancer therapy (Endpoints News)

February 19, 2020

The results were clear: Naptumomab estafenatox failed to prolong overall survival for renal cell carcinoma patients in a large trial, definitively enough that Active Biotech effectively shelved it in 2013.

But three years later NeoTX, a scavenger startup that had been digging through drugs that failed in hopes of finding a subpopulation with a biomarker that the original developer had missed, stumbled upon the data and saw the unexpected gem they were looking for.

Asher Nathan
“Their Phase I data was stellar, great Phase I, and then they had this Phase II that failed primarily because they added the wrong drug,” Asher Nathan, CEO and co-founder of NeoTX, told Endpoints News as he unveils $45 million in new financing.

Interferon alpha was “absolutely the wrong drug” to combine with naptumomab estafenatox as it negated certain qualities of the experimental fusion protein, Nathan said. More importantly, Active Biotech didn’t really know just the kind of potential they had in a platform tech that binds to the tumor and coat it with a bacterial “superantigen” that attracts an immune attack.

“This is a natural immune response as opposed to if you look at other technologies like bispecifics, where they gauge CD3 molecules, that’s something you’ll never find in nature,” Nathan said.

So the Israeli biotech licensed the drug from Active for $250,000 upfront, and has been collaborating to start a Phase I that tests a combo of nap and AstraZeneca’s checkpoint drug, Imfinzi (durvalumab).

Roger Kornberg
Roger Kornberg, a Nobel laureate, Stanford cancer researcher and longtime friend of Nathan’s, helped guide the company’s pivot to focus on this approach, which they call selective T cell redirection or STR. And longtime Bristol-Myers Squibb exec Marcel Rozencweig is onboard as CMO, leading a small office in Princeton, New Jersey in preparation for a trial expansion to the US.

They are enrolling patients with a wide range of solid tumors to the Phase Ib dose escalation trial — from pancreatic adenocarcinoma and ovarian cancer to prostate cancer and triple negative breast cancer — as naptumomab targets the oncofetal antigen 5T4.

Other drugmakers have mounted efforts to hone in on 5T4, ranging from Sanofi and Oxford Biomedica’s Phase III cancer vaccine to Pfizer’s early-stage antibody-drug conjugate to Genmab’s preclinical CD3/5T4 bispecific.

Marcel Rozencweig
NeoTX is also working on a second candidate hitting a different target specifically tailored to glioblastoma. They’ve brought David Reardon of Dana Farber on for that program, which also utilizes the bacterial component.

The team of around 20 has some powerful — if unconventional — backers. For the Series C, they enticed “one of the top 10 richest people in the world,” former Blackstone vice chairman Tomilson Hill, American businessman Paul Marinelli as well as Korean investor Andrew Kim.

Credit: Amber Tong

NeoTX Therapeutics’s CEO, Asher Nathan, interviewed by Karen Jagoda on the Empowered Patient Podcast

January 9, 2020
Rehovot, Israel

NeoTX was featured on a popular patient radio podcast.
Dr. Asher Nathan, CEO of NeoTX talks about the company’s work developing immunotherapies for a wide range of solid tumors using their proprietary Selective T Cell Redirection (STR) platform. This technology enables therapies that bind a genetically engineered super antigen to the tumor surface which trigger a native, controlled immune response that can kill the cancer with potentially fewer side effects than currently available therapies. Asher discusses the company’s lead STR molecule, NAP, which is being developed to treat advanced cancers. NAP, which has potential as both a monotherapy and in combination with checkpoint inhibitors, is currently in a Phase 1B clinical trial in collaboration with AstraZeneca.
Download the transcript here

T Cell Redirection Drives Natural Immune Response Against Solid Tumors with Asher Nathan NeoTX (Empowered Patient Podcast)

January 8, 2020

Dr. Asher Nathan, CEO of NeoTX talks about the company’s work developing immunotherapies for a wide range of solid tumors using their proprietary Selective T Cell Redirection (STR) platform.  This technology enables therapies that bind a genetically engineered super antigen to the tumor surface which trigger a native, controlled immune response that can kill the cancer with potentially fewer side effects than currently available therapies.  Asher discusses the company’s lead STR molecule, NAP, which is being developed to treat advanced cancers.  NAP, which has potential as both a monotherapy and in combination with checkpoint inhibitors, is currently in a Phase 1B clinical trial in collaboration with AstraZeneca.

Credit: empoweredpatientradio.com

T Cell Redirection Drives Natural Immune Response Against Solid Tumors with Asher Nathan NeoTX (Empowered Patient Podcast)

January 8, 2020

NeoTX commences dosing in Phase Ib trial of naptumomab (Clinical Trials Arena)

October 28, 2019

NeoTX Therapeutics has dosed the first patient in a Phase Ib clinical trial of a naptumomab estafenatox and Imfinzi (durvalumab) combination for the treatment of solid tumours.

Designed as immunotherapy, naptumomab stimulates the immune system to identify and kill tumour cells. The drug triggers certain T cells outside the tumour microenvironment and redirects the immune cells to attack the tumours.

In preclinical studies involving different tumour models, naptumomab demonstrated the potential for a synergistic effect with checkpoint inhibitors.

NeoTX Therapeutics licensed the drug from Active Biotech in 2016. As part of the licence agreement, NeoTX has to carry out the development and commercialisation of the drug in oncology indications.

Imfinzi is a checkpoint inhibitor developed by AstraZeneca. It is a human monoclonal antibody that inhibits the PD-L1 interaction with PD-1 and CD80.

Imfinzi has approvals for the treatment of unresectable, stage III non-small cell lung cancer (NSCLC) and advanced bladder cancer. The drug is also being developed for various other solid tumours.

The open-label, multi-centre, dose-finding Phase Ib trial will investigate the safety and tolerability of naptumomab plus Imfinzi for treating advanced or metastatic tumours in around 45 patients who received prior therapies.

Credit: www.clinicaltrialsarena.com

NeoTX is featured in Haaretz Magazine

December 3, 2017

NeoTX, an Immuno-Oncology drug development company, was featured in the December edition of their business magazine, highlighting Anyara

Anyara is a TTS (Tumor Targeting Superantigen) compund that enhances the ability of the immune system to recognize a tumor.
See the online version on page 41 here. For the pdf download, please click here.