Highlight Therapeutics

Press Release.

Final results of SPOTLIGHT203 phase 2 study demonstrate new approach to second line treatment for melanoma

Madrid, Spain, 15 March, 2022 – Highlight Therapeutics, (“Highlight”), a clinical-stage biopharmaceutical company developing RNA-based therapies against cancer, today announced an oral presentation at the Combination Immunotherapy Clinical Trials Plenary Session at the American Association for Cancer Research (AACR) Annual Meeting 2022, taking place April 8-13, 2022 in New Orleans, Louisiana. The Company will also present three posters.

SESSION TITLE: Combination Immunotherapy Clinical Trials

PRESENTATION TITLE: CT014

Efficacy of intratumoral BO-112 with systemic pembrolizumab in patients with advanced melanoma refractory to anti-PD-1-based therapy: Final results of SPOTLIGHT203 phase 2 study

PRESENTER: Ivan Marquez-Rodas

DATE: April 12, 2022

TIME: 1015 –1215 PM CT

LOCATION: New Orleans Convention Center, Exhibit Halls B-C

Highlight will also present the following posters at AACR:

PRESENTATION TITLE: Correlation of biomarkers and clinical benefit of intratumoral BO112 and pembrolizumab in patients with anti PD1 refractory melanoma

DATE: April 11, 2022

TIME: 9:00 AM – 12:30 PM

LOCATION: New Orleans Convention Center

PRESENTATION TITLE: Radiomic features in tumor assessment, preliminary results from a phase 2 study of intratumoral administration of BO-112 with pembrolizumab in patients with anti PD1 refractory melanoma

DATE: April 11, 2022

TIME: 9:00 AM – 12:30 PM

LOCATION: New Orleans Convention Center

For more information, please contact:

Highlight Therapeutics S. L. info@highlighttherapeutics.com
Marisol Quintero, CEO

Mo PR Advisory Tel: +44 (0) 7876 444977 / 07860 361746
Mo Noonan/Jonathan Birt

Notes to editors

About Highlight Therapeutics

Highlight Therapeutics is a private, clinical-stage company dedicated to unlocking the full potential of immuno-oncology. Our lead drug candidate BO-112 is a best-in-class RNA-based therapy which has been demonstrated to initiate a powerful immune response, leveraging a unique multi-target approach to turn ‘cold’ tumors ‘hot’ and therefore visible to the immune system. It has the potential to rescue patients who are resistant to current checkpoint inhibitor therapy, a very large market opportunity. BO-112 is currently being investigated in a range of clinical trials as a monotherapy and in combination with checkpoint inhibitors. In addition to in-house research, Highlight Therapeutics has a number of external collaborators, including Merck & Co and UCLA.

For more information, please visit www.highlighttherapeutics.com

Press Release.

Intratumoral co-injection of BO-112 and a STING agonist synergize to achieve local and distant anti-tumor efficacy

Pre-clinical study data follow publication of positive Phase 2 results of BO-112 + pembrolizumab in melanoma at SITC

Madrid, Spain, 2 December, 2021 – Highlight Therapeutics, (“Highlight”), a clinical-stage biopharmaceutical company developing RNA-based therapies against cancer, and the Spanish research institute Cima Universidad de Navarra today announced that positive results from a pre-clinical study of intratumoral administration of BO-112 with a STING agonist have been published in the Journal for ImmunoTherapy of Cancer (JITC, Impact Factor 13.75). 1

BO-112 is a dsRNA agonist which is in development to target anti-PD1 resistance. Positive preliminary results of a phase 2 study of intratumoral administration of BO-112 with pembrolizumab in patients with advanced melanoma that have progressive disease on anti-PD-1-based therapy were presented at The Society for Immunotherapy of Cancer (SITC) in Washington, D.C. on Nov. 12.

Results of a pre-clinical in vivo study of intra-tumoral co-injections of BO-112 and the DXMAA STING agonist conducted by Cima demonstrated synergistic efficacy with the ability to eradicate distant, uninjected tumor lesions. The combination of BO-112 and DMXAA was chosen because of its excellent efficacy, and the requirements for antitumor effects were studied on selective depletion of immune cell types and in gene-modified murine strains lacking BATF3, IFNAR or STING.

“These results, following the positive Phase 2 data on the combination of BO-112 and anti-PD1 therapies, are very encouraging,”

said Dr. Marisol Quintero, CEO of Highlight Therapeutics.

“We have been collaborating with Dr. Melero to better understand BO-112’s Mode of Action. The main objective has been to achieve both local control of the disease and, more importantly, efficacy against distant tumor lesions. The work published in the Journal for ImmunoTherapy of Cancer shows that co-injections of BO-112 and a STING agonist attain synergistic efficacy, enabling distant uninjected tumor lesions to be eradicated. There may also be further opportunities involving irradiation of locally injected lesions and we look forward to continuing this work.”

“We believe this combined intratumoral approach should be feasible in the clinic, since both BO-112 and several STING agonists have been injected into patients’ tumors in clinical trials. We have consistently observed synergistic therapeutic effects on a variety of transplantable murine tumor models, showing complete regressions of the injected and non-injected concomitant tumor lesions”

commented Dr. Ignacio Melero, senior researcher in immunotherapy at Cima and co-director of the Department of Immunology at Clínica Universidad de Navarra.

Abstract published in JITC
Background BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid that acting on TLR3, MDA5 and PKR elicits rejection of directly injected transplanted tumors, but has only modest efficacy against distant untreated tumors. Its clinical activity has also been documented in early phase clinical trials. The DMXAA STING agonist shows a comparable pattern of efficacy when used via intratumoral injections.
Methods Mice subcutaneously engrafted with bilateral MC38 and B16.OVA-derived tumors were treated with proinflammatory immunotherapy agents known to be active when intratumorally delivered. The combination of BO-112 and DMXAA was chosen given its excellent efficacy and the requirements for antitumor effects were studied on selective depletion of immune cell types and in gene-modified mouse strains lacking BATF3, IFNAR or STING. Spatial requirements for the injections were studied in mice bearing three tumor lesions.
Results BO-112 and DMXAA when co-injected in one of the lesions of mice bearing concomitant bilateral tumors frequently achieved complete local and distant antitumor efficacy. Synergistic effects were
contingent on CD8 T cell lymphocytes and dependent on conventional type 1 dendritic cells, responsiveness to type I IFN and STING function in the tumor-bearing host. Efficacy was preserved even if BO-112 and DMXAA were injected in separate lesions in a manner able to control another untreated third-party tumor. Efficacy could be further enhanced on concurrent PD-1 blockade.

Conclusion Clinically feasible co-injections of BO-112 and a STING agonist attain synergistic efficacy able to eradicate distant untreated tumor lesions.

Next steps in the development of BO-112 include:

• Initiation of a pivotal Phase 3 study in 2nd-line melanoma is planned in 2022 following discussions with regulatory agencies in the US and Europe

• Highlight Therapeutics has initiated strategic partnerships discussions with anti-PD1 companies interested in enhancing their anti-PD1 market potential

• Initial data from a sponsor-initiated Phase 1B trial by UCLA evaluating BO-112 + pembrolizumab in anti-PD1 resistant hepatocellular carcinoma currently recruiting patients is expected in 2022

1. Alvarez M, Molina C, De Andrea CE, et al Intratumoral co-injection of the poly I:C-derivative BO-112 and a STING agonist synergize to achieve local and distant anti-tumor efficacy Journal for ImmunoTherapy of Cancer 2021;9:e002953. doi: 10.1136/jitc-2021-002953
https://jitc.bmj.com/content/9/11/e002953.info

For more information, please contact:

Highlight Therapeutics S. L.
info@highlighttherapeutics.com
Marisol Quintero, CEO
Mo PR Advisory
Tel: +44 (0) 7876 444977 / 07860 361746

Mo Noonan/Jonathan Birt
Cima Universidad de Navarra
mphuarte@unav.es
Maria Pilar Huarte
Notes to editors

About Highlight Therapeutics

Highlight Therapeutics, formerly known as Bioncotech Therapeutics, is a private, clinical-stage company dedicated to unlocking the full potential of immuno-oncology. Our lead drug candidate BO-112 is a best-in-class RNA-based therapy which has been demonstrated to initiate a powerful immune response, leveraging a unique multi-target approach to turn ‘cold’ tumors ‘hot’ and therefore visible to the immune system. It has the potential to rescue patients who are resistant to current checkpoint inhibitor therapy, a very large market opportunity. BO-112 is currently being investigated in a range of clinical trials as a monotherapy and in combination with checkpoint inhibitors. In addition to in-house research, Highlight Therapeutics has a number of external collaborators, including Merck & Co and UCLA.

For more information, please visit www.highlighttherapeutics.com

About Cima Universidad de Navarra

Cima Universidad de Navarra is a biomedical research institution of the Universidad de Navarra. Our mission is to conduct translational research of excellence, based on novel biological knowledge and aimed at finding therapeutic solutions to patients’ needs. To translate the results of basic research into clinical applications, Cima has a Translation and Transfer unit that seeks to establish collaborations with biotechnology and pharmaceutical companies to ensure patients can benefit from scientific innovation.

We specialize in cancer, heart and liver diseases, immunotherapy and gene therapy research.

More information: www.cima.unav.edu/en

Press Release.

Highlight Therapeutics announces positive preliminary results from Phase 2b study of BO-112 + anti-PD1 in confirmed anti-PD1 progressor melanoma patients at SITC

Breakthrough cancer treatment shows best-in-class potential to open up 2nd-line immunotherapy market to anti-PD1 resistant patients

• BO-112 demonstrates potential as best-in-class therapy to overcome anti-PD1 resistance in melanoma patients whose disease has progressed on prior anti-PD-1 treatment

• Primary endpoint met with a 27% Overall Response Rate (ORR), 8% Complete Responses (CR) & 65% Disease Control Rate (DCR) substantially exceeding current standard of care; further improvements anticipated over one year follow up

• Hard-to-treat mucosal melanoma patients achieved 66% ORR and 100% DCR

• Durable responses and manageable safety profile, with no patients discontinuing due to adverse events

• Preparation for pivotal trial based on FDA guidance underway; potential for use in multiple solid cancers resistant to anti-PD1 inhibitors, and with different anti-PD1 combinations

Madrid, Spain, 12 November, 2021 – Highlight Therapeutics, (“Highlight”), a clinical-stage biopharmaceutical company developing RNA-based therapies against cancer, today announced positive preliminary results of a Phase 2 study of intratumoral administration of BO-112 with pembrolizumab in patients with advanced melanoma whose disease had progressed on first-line anti-PD1-based therapy. BO-112 is a dsRNA agonist targeting anti-PD1 resistance, which has been successfully tested in several previous Phase 1b studies.

Initial results of the study were presented today (12th November) in a late-breaking session at The Society for Immunotherapy of Cancer (SITC) 36th Annual Meeting in Washington DC, Nov. 10–14, 2021. (LBA Poster Abstract (961): Preliminary results of a phase 2 study of intratumoral administration of BO-112 with pembrolizumab in patients with advanced melanoma that have progressive disease on anti-PD-1-based therapy, presented in the Poster Hall in Washington, D.C. and the virtual ePoster Hall beginning Friday, Nov. 12 at 7 a.m. EST).

“These are potentially game-changing results showing that BO-112 can rescue melanoma patients who have failed first-line immune-therapy with anti-PD1,”

said Dr Carlos Paya, Executive Chairman of Highlight Therapeutics.

“Anti-PD1 based immunotherapy has revolutionized oncology treatments, but only a fraction of patients initially respond and many of these patients progress thereafter. These initial Phase 2 results show that BO-112 combined with a leading PD1 inhibitor rescue around 65% of anti-PD1 failing patients, making many of them respond to the combined treatment. These much-anticipated outcomes demonstrate BO-112’s potential as a best-in-class therapy for melanoma patients whose disease has progressed on prior anti-PD1 treatment, and we now look forward to further clinical studies, not only in melanoma but in other major tumor types in which anti-PD1 resistance is also an issue.”

Anti-PD1 therapies are valued at approximately $24 billion1 and are used across most solid tumors but currently fewer than 20% of all cancer patients benefit from first-line anti-PD1 treatment. BO-112 in combination with anti-PD1 therapy is designed to resensitize tumors to anti-PD1 treatment through improved antigen presentation, enhanced T-cell infiltration and increased MHC-1 and PDL1 expression by the tumor itself.

“This initial data is very encouraging and has the potential to change medical practice,”

said Dr. Marisol Quintero, CEO of Highlight Therapeutics.

“The preliminary ORR of 27%, including 8% Complete Responses, already exceeds current standard of care, such as the use of anti-CTLA-4. Based on the mode of action and experience from previous BO-112 Phase 1 studies, additional follow-up of these patients is expected to deliver further improvements in ORR. We are also encouraged by the excellent safety profile, with no patients discontinuing the study due to adverse events. Highlight Therapeutics is in the planning stage of a pivotal Phase 3 trial, due to begin in 2022, and we look forward to opening discussions with potential partners to explore combinations with anti-PD1s.”

Highlight Therapeutics and Merck, known as MSD outside the United States and Canada, conducted an open-label, single arm study to evaluate the efficacy & safety of intra-tumoral administration of BO-112 + pembrolizumab in mucosal, acral and cutaneous melanoma patients whose disease had progressed, confirmed by two consecutive CT scans. The study recruited 42 patients in France and Spain, with recruitment completed by August 24, 2021. Patients included those with high LDH levels, which are often associated with poor response rates and have been excluded from comparable clinical trials.

The preliminary analysis shows:

• Primary endpoint (ORR by independent reviewer) has been met

• With a median follow up of three months, there is a clear clinical benefit in patients with confirmed anti-PD1-resistant melanoma, with a 27% ORR and a 65% DCR, superior to 2nd line Standard of Care in stage III/IV melanoma of ~8% (continuing with anti-PD1 Ab) or 13% (second line ipilimumab).

• Three hard-to-treat mucosal melanoma patients have achieved an ORR of 66% and DCR of 100%

• High baseline LDH levels (>3xULN) predict progressive disease

• Responses and SD are durable

• Study treatment has a manageable safety profile, with no patients discontinuing due to adverse events

Next steps in the development of BO-112 include:

• Initiation of a pivotal Phase 3 study in 2nd-line melanoma is planned in 2022 following discussions with regulatory agencies in the US and Europe

• Highlight Therapeutics has initiated strategic partnerships discussions with anti-PD1 companies interested in enhancing their anti-PD1 market potential

• Initial data from a sponsor-initiated Phase 1B trial by UCLA evaluating BO-112 + pembrolizumab in anti-PD1 resistant hepatocellular carcinoma currently recruiting patients is expected in 2022

1. IQVIA Global Oncology Report 2020

For more information, please contact:

Highlight Therapeutics S. L.                      info@highlighttherapeutics.com
Marisol Quintero, CEO

Mo PR Advisory                                       Tel: +44 (0) 7876 444977 / 07860 361746
Mo Noonan/Jonathan Birt

Consilium Strategic Communications     Tel: +44 7921 697654
Chris Gardner                                            cgardner@consilium-comms.com

Notes to editors

About Highlight Therapeutics

Highlight Therapeutics, formerly known as Bioncotech Therapeutics, is a private, clinical-stage company dedicated to unlocking the full potential of immuno-oncology. Our lead drug candidate BO-112 is a best-in-class RNA-based therapy which has been demonstrated to initiate a powerful immune response, leveraging a unique multi-target approach to turn ‘cold’ tumors ‘hot’ and therefore visible to the immune system. It has the potential to rescue patients who are resistant to current checkpoint inhibitor therapy, a very large market opportunity. BO-112 is currently being investigated in a range of clinical trials as a monotherapy and in combination with checkpoint inhibitors. In addition to in-house research, Highlight Therapeutics has a number of external collaborators, including Merck & Co and UCLA.

For more information, please visit www.highlighttherapeutics.com

Press Release.

Madrid, Spain, 14 April, 2021 – Highlight Therapeutics, (“Highlight”), a clinical-stage biopharmaceutical company developing RNA-based therapies against cancer, today announced that data from Phase 2 studies of its RNA-based immunotherapy BO-112 will be presented as posters at the American Association for Cancer Research (AACR) Virtual Annual Meeting 2021, April 10-15 and May 17-21.

The e-poster presentations, which are available for browsing on from April 10, 2021, through June 21, 2021, are entitled:

• Phase IIa open-label clinical study of intratumoral administration of BO-112 in combination with pembrolizumab in subjects with liver metastasis from colorectal cancer or gastric/gastro-oesophageal junction cancer (Abstract number 5289)

• Phase 2 clinical study to evaluate the efficacy and safety of intratumoral BO-112 in combination with pembrolizumab in patients with advanced melanoma that have progressive disease on anti-PD-1-based therapy (Abstract number 4936)

• BO-112 as a modifier of the tumor microenvironment for liver metastases (Abstract number 994)

• A phase I study of intratumoral BO-112 and nivolumab for resectable soft tissue sarcoma (Abstract number 5273)

Marisol Quintero, CEO of Highlight Therapeutics, commented:

“Data to be presented at AACR include promising results from one of our Phase 2 studies testing the combination of BO-112 + pembrolizumab in colorectal cancer microsatellite stable patients with liver metastases. The data demonstrates that BO-112 can be injected directly into liver metastases, triggering a potent change in the tumor micro-environment, characterized by increased numbers of CD8-T cells and increased expression of PDL-1.”

Highlight Therapeutics aims to use this approach to modify the suppressive environment of liver tumors that limits the activity of immunotherapy. (Abstracts 5289 and 994).

Highlight Therapeutics is also presenting data from its Phase 2 trial for patients that have progressed to anti-PD-1-based therapy in refractory advanced malignant melanoma.

Marisol Quintero added:

“Results from Phase 1 studies showed a clear signal in the melanoma resistant population, prompting us to develop this trial with a higher dose of BO-112 and a more frequent injection scheme designed to maximize the possibility of seeing responses in this setting. Our aim is to demonstrate how BO-112 can extend the benefit of immunotherapy in patients that have progressed to anti-PD1-based therapies. This concept could be later on applied to other indications.” (Abstract 4936).

For more information, please contact:

Highlight Therapeutics S. L.
info@highlighttherapeutics.com
Marisol Quintero, CEO

Mo PR Advisory
Tel: +44 (0) 7876 444977 / 07860 361746
Mo Noonan/Jonathan Birt

Notes to editors

About Highlight Therapeutics

Highlight Therapeutics, formerly known as Bioncotech Therapeutics, is a private, clinical-stage company
dedicated to unlocking the full potential of immuno-oncology. Our lead drug candidate BO-112 is a best-inclass
RNA-based therapy which has been demonstrated to initiate a powerful immune response, leveraging
a unique multi-target approach to turn ‘cold’ tumors ‘hot’ and therefore visible to the immune system. It has
the potential to rescue patients who are resistant to current checkpoint inhibitor therapy, a very large market
opportunity. BO-112 is currently being investigated in a range of clinical trials as a monotherapy and in
combination with checkpoint inhibitors. In addition to in-house research, Highlight Therapeutics has a
number of external collaborators, including Merck & Co and UCLA.
For more information, please visit www.highlighttherapeutics.com

Press Release.

• Trial will examine administration of Highlight’s BO-112 in combination with an anti-PD1 in unresectable or metastatic melanoma patients
• Recruitment has already begun across 19 top-level centers in Spain and France
• No delays to recruitment despite the persistent challenges encountered during the COVID-19 pandemic

Madrid, Spain, 2 March, 2021 – Highlight Therapeutics, (“Highlight”), a clinical-stage biopharmaceutical company developing RNA-based therapies against cancer, and Pivotal, a Europe-wide full-service CRO, today announced that the first patients have been recruited in a Phase IIa study to assess Highlight’s lead program BO-112 in combination with an anti-PD1 therapy, in patients with unresectable or metastatic melanoma that have previously progressed to checkpoint inhibitors

Melanoma is the most malignant tumor of the skin although it can be seldom found in other organs. Incidences of this tumor are rapidly increasing in western countries and, once disseminated, it has been considered an incurable disease with limited therapeutic options. Recently, immunotherapy with anti-PD1 (checkpoint inhibitors) showed encouraging results with 30-36% patients alive at 5 years. Unfortunately, the median PFS (progression free survival) is less than 12 months, mainly due to primary or acquired resistance to anti-PD1 treatment, and most of those patients will die due to the tumor or its complications.

“This Phase IIa study is an important step forward in our strategy to develop effective cancer therapies which can be used in combination with checkpoint inhibitors. We are looking to produce a better immunological response in anti-PD1 therapy-sensitive patients, and to induce or maintain responses for those patients that progress or are initially treatment-resistant. BO-112 has the potential to be employed from the beginning of disease treatment and we believe it offers patients a resistant status after immunological treatment,”

said Dr. Marisol Quintero, PhD, CEO of Highlight Therapeutics.

“We are encouraged by the effectiveness already seen in previously treated melanoma patients in the phase I study with BO-112 and we are pleased to be working once more with the highly experienced and dedicated team at Pivotal.”

This Phase IIa, open-label clinical study is a non-comparative trial implemented in 19 sites across Spain and France. The protocol will include a minimum of 40 non-resectable melanoma patients. This is the third trial with BO-112, following initiation of the phase I trial in 2016. In 2020, a second trial was initiated in gastrointestinal tumors from which the first cohorts have already been successfully completed, and the recruitment of this phase IIa trial has now been initiated in melanoma despite the obstacles presented due to the COVID-19 pandemic.

The study will evaluate the anti-tumoral activity and systemic exposure of repeated intratumoral injections of BO-112 into a tumoral lesion, in combination with intravenously administered anti-PD1. BO-112 has intrinsic anti-tumoral effects, but interestingly acts on several mechanisms involved in resistance to Checkpoint inhibitors.

“The excellence in clinical research of the clinical investigators´ teams, together with Pivotal’s infrastructure and vast experience in the implementation and performance of innovative early phases clinical trials, will allow us to accelerate the research and to quickly test this new treatment regimen,”

said Dr. Lourdes Huarte, PhD, Senior Vice President of Regulatory and Clinical Operations at Pivotal.

“The challenge of this trial was to swiftly implement the study and activate its recruitment in a period negatively impacted by the COVID-19 pandemic. We are delighted to have diligently achieved our first milestone with the recruitment of the first patients in this trial.”

About Highlight Therapeutic

Highlight Therapeutics, formerly known as Bioncotech Therapeutics, is a private, clinical-stage company dedicated to unlocking the full potential of immuno-oncology. Our lead drug candidate BO-112 is a best-in-class RNA-based therapy which has been demonstrated to initiate a powerful immune response, leveraging a unique multi-target approach to turn ‘cold’ tumors ‘hot’ and therefore visible to the immune system. It has the potential to rescue patients who are resistant to current checkpoint inhibitor therapy, a very large market opportunity. BO-112 is currently being investigated in a range of clinical trials as a monotherapy and in combination with checkpoint inhibitors. In addition to in-house research, Highlight Therapeutics has a number of external collaborators, including Merck & Co and UCLA
For more information, please visit www.highlighttherapeutics.com; or

Contacts Dr. Marisol Quintero CEO at Highlight Therapeutics     info@highlighttherapeutics.com
Mo PR Advisory    Tel: +44 (0) 7876 444977 / 07860 361746
Mo Noonan/Jonathan Birt

About Pivotal

Pivotal was founded in 2001 by Dr. Ibrahim Farr on the principle that strategic medical advice and support should be the backbone of all clinical trials. After working for over two decades in the pharmaceutical industry, Dr. Farr recognized the need for a medium-sized CRO with a solid internal medical franchise that could act not only as the “doers” but also as the “co-thinkers” for their clients, through its strategic scientific advice. To date, we are the trusted adviser and counsellor for many companies to deliver maximum value in their drug and medical devices development programs. We are a leading privately held European CRO and, since inception, we have experienced a fast and steady organic growth in Europe.
Pivotal´s client portfolio spans major pharmaceutical, biotechnological, medical device and nutrition companies, as well as independent investigators and cooperative groups. We have long-standing relations with over 200 clients. Pivotal has extensive experience across major therapeutic areas and phases I to IV. Our highly customized teams bring to each client a combination of broad industry knowledge and operational excellence, to offer our clients fresh perspectives and breakthrough business insights. Additionally, we have built a strong oncology, innovative therapies, infectious diseases, vaccines, rare diseases and early phases hub that enables us to tackle our customers most difficult challenges, turning recommendations into concrete actions. By remaining true to our core principles and values, our vision is to become our client’s preferred outsourcing solution partner.
For more information, please visit www.pivotalcr.com; or
Contact Ms Natalia Farr at Pivotal natalia.farr@pivotalcr.com

Press Release.

Second collaboration with MSD to evaluate combination of BO-112 and KEYTRUDA®

•    New research studies may further accelerate delivery of novel treatment strategies for melanoma

Madrid, Spain – September 2, 2020: Highlight Therapeutics (“Highlight”), a clinical-stage biopharmaceutical company developing RNA-based therapies against cancer, announces it has entered into a second Phase II trial collaboration with a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, U.S.A., known as MSD outside the U.S. and Canada.

The collaboration will focus on the Phase II evaluation of the combination of BO-112, Highlight’s lead program, and KEYTRUDA® (pembrolizumab), MSD’s anti-PD-1 therapy, in patients that have progressed on anti-PD-1-based therapy in refractory advanced malignant melanoma.

The incidence of malignant melanoma is estimated to be 3-5 cases per 100,000 individuals in Europe. Activating therapeutic anti-tumor immunity by the modulation of the host immune system has become a key approach for treating melanoma. Antagonistic monoclonal antibodies (mAb) against immune inhibitory molecules such as CTLA4 (cytotoxic T-lymphocyte associated protein 4) and PD-1 (programmed death receptor-1) have improved the prognosis of patients with malignant melanoma and have been incorporated into oncology treatment guidelines as a standard of care. However, most patients treated in this way do not achieve a clinical response and many of those who do respond eventually develop progressive disease.

The trial, named Spotlight 203, will evaluate the combination of stimulation of the innate immune system by direct intra-tumoral administration of BO-112, combined with systemic administration of pembrolizumab, based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as the percentage of patients achieving a complete response or partial response as primary endpoint.

Spotlight 203 will also seek to further characterize the clinical activity of intra-tumoral BO-112 in combination with pembrolizumab by evaluating disease control rates, duration of response, progression-free and overall survival, as well as safety, tolerability and pharmacokinetics. A total of 40 patients are planned to be enrolled. The sample size for a subsequent randomized portion of the study will be determined based on efficacy results.

Marisol Quintero, CEO of Highlight Therapeutics, commented:

“Spotlight 203 is designed to address the high unmet need of patients with unresectable stage III or IV melanoma who have failed anti-PD-1 therapy. Phase 1 data suggest the potential of BO-112 to sensitize the immune system against the tumor, including enhanced sensitivity to anti-PD-1 treatment. Based on clinical and pre-clinical studies, we believe intra- tumoral BO-112 has the potential to overcome resistance to anti-PD-1 therapy. We are pleased to build on our fruitful collaboration with MSD, whose extensive expertise in immune-oncology makes them the ideal partner.

“This partnership seeks to accelerate the development of therapies for patients with malignant melanoma. We are delighted to commence Spotlight 203 and to be able to combine our capabilities to accelerate the research of medicines in diseases with such a poor prognosis.”

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ. A Phase 2 clinical study of intra-tumoral BO-112 in combination with pembrolizumab in patients with liver metastases from colorectal or gastric/gastro-esophageal junction cancer is also currently underway.

For more information, please contact:

Highlight Therapeutics S. L.    info@highlighttherapeutics.com

Marisol Quintero, CEO
Mo PR Advisory    Tel: +44 (0) 7876 444977 / 07860 361746
Mo Noonan/Jonathan Birt

Notes to Editors

About melanoma
Almost 288,000 new cases of melanoma and more than 60,000 deaths were estimated worldwide in 2018 [Ferlay 2019]. In North America, melanoma is the fifth most common cancer in males and sixth most common cancer in females [Siegel 2018]. In the U.S, it is estimated that more than 100,000 patients will be diagnosed with melanoma in 2020, with almost 7,000 deaths recorded. Advanced or metastatic melanoma (unresectable Stage III, Stage IV) remains a lethal disease with a high proportion of patients resistant to approved therapies. There are currently limited treatment options for patients who progress on targeted therapy or immunotherapy, creating a high unmet need for novel therapies for advanced melanoma patients who have failed existing treatments.

About Highlight Therapeutics
Highlight, formerly known as Bioncotech Therapeutics S.L, is a private, clinical-stage company dedicated to unlocking the full potential of immuno-oncology. Its lead drug candidate BO-112 is a best-in-class RNA-based therapy which has been demonstrated to initiate a powerful immune response, leveraging a unique multi- target approach to turn ‘cold’ tumors ‘hot’ and therefore visible to the immune system. It has the potential to rescue patients who are resistant to current checkpoint inhibitor therapy, a very large market opportunity. BO-112 is currently being investigated in a range of clinical trials as a monotherapy and in combination with checkpoint inhibitors. In addition to in-house research, Highlight Therapeutics has a number of external collaborators, including Merck & Co and UCLA.

Press Release.

Dr Ralph Weichselbaum, Dr.Antoni Ribas & Michael Docherty appointed to SAB

Company renamed to Highlight Therapeutics

Madrid,  Spain –April  17, 2020: Highlight Therapeutics (“Highlight”), a clinical-stagebio pharmaceutical company developing RNA-based therapies against cancer,announces the appointment of Carlos Paya, MD, PhD,as Executive Chairman with immediate effect.The Company has also significantly expanded its Advisory Board with a number of internationally-renowned scientific and industry leaders.  In line with these changes, the  Company has  been  renamed from Bioncotech Therapeutics  to  Highlight Therapeutics – see separate press release.

Marisol  Quintero, CEO of Highlight, said:

“Dr Paya’s impressive industry experience,  his  track  record  of guiding biotech companies through product development to global launch and his extensive reach with both scientists and investors will all be of great assistance to Highlight at this important point in our development. In  addition,  we have significantly expanded our Advisory  Board with distinguished scientists and  industry specialists of the highest caliber. These key appointments provide Highlight with the broad range of skills and know how to drive our ambition to unlock thepotential of immunotherapy for many more patients.”

Dr. Paya has a distinguished track record of leadership in large-cap pharma and mid-cap biotech and start-up companies, with a focus on strategic execution, pipeline growth, product life cycle management and global product launches, as well as a number of successful public and private fundraises.

He is a director of Mallinckrodt Pharmaceuticals and of Fluidigm Corporation. Previously, he was president, chief executive officer and board member of Immune Design Corp., a late-stage immunotherapy company, from  May  2011  until  its  acquisition  by  Merck  &  Co.,  Inc.  in  April  2019.He held  leadership  roles  at Elan Pharmaceuticals and Eli Lilly and Co. in discovery research and clinical development. Prior to  his  industry roles, Dr.  Paya spent  nearly  a  decade  at  the  Mayo  Clinic-Rochester, including as professor of medicine, immunology and pathology and vice dean of the clinical investigation program.

Dr Paya received his medical and doctorate degrees from the Universidad Complutense of Madrid Medical School, and completed his specialty training in Internal Medicine, Infectious Diseases and Immunology at the Mayo Graduate  School of  Medicine.  He was a research scientist in a  post-doctoral  position at Institute Pasteur in Paris and completed the advanced management program at the University of Chicago’s Booth School of Business.

The Company’s Scientific Advisory Board has expanded and now comprises:

Ralph R. Weichselbaum MD

• Professor of Radiation & Cellular OncologyChair, Department of Radiation & Cellular Oncology, University of Chicago
• Made discoveries in basic signal transduction after ionizing radiation exposure &, in separate studies, discovered that mechanisms of radiation resistance/sensitivity are mediated by cytokine activation in tumors
• Currently investigating the relationship between radiotherapy & immunotherapy

Antoni Ribas MD, PhD

• Professor of Medicine, Professor of Surgery & Professor of Molecular & Medical Pharmacology at UCLA
• Director of Tumor Immunology Program at Jonsson Comprehensive Cancer Center
• Director of Parker Institute for Cancer Immunotherapy Center, UCLA
• Chair of SWOG Melanoma Committee; member of American Society of Clinical Investigation
• Recipient of AACR Richard & Hinda Rosenthal Award & NCI Outstanding Investigator Award

Michael Doherty

• Led Global Regulatory Affairs function at Roche & launched first oncology portfolio with a franchise of monoclonal antibodies and targeted medicines
• Member of the Roche portfolio committee from 2002 to 2016
• Prior positions: Global Head, Pharma Regulatory Affairs
• Hoffmann La-Roche Ltd., Basel/Genentech, San Francisco
• Head Product Development Foundation Medicine

For more information, please contact:

Highlight Therapeutics, Marisol Quintero, CEO info@highlight.com

Mo PR Advisory, Mo Noonan / Jonathan Birt Tel: +44 (0) 7876 444977/ 07860 361746

Notes to Editors

About Highlight Therapeutics

Highlight, formerly known as Bioncotech Therapeutics S.L, is a private, clinical-stage company dedicated to unlocking the full potential of immuno-oncology. Itslead drug candidate BO-112 is a best-in-class RNA-based therapy which has been demonstrated to initiate a powerful immune response, leveraging aunique multi-target approach to turn ‘cold’ tumors ‘hot’ and therefore visible to theimmune system. It has the potential to rescue patients who are resistantto current checkpoint inhibitor therapy, a very large market opportunity. BO-112 is currently being investigated in a range of clinical trials as a monotherapy and in combination with checkpoint  inhibitors.  In  addition  to  in-house  research,  Highlight  Therapeutics  has  a  numberof  external collaborators, including Merck & Co and UCLA

Press Release.

Madrid,  Spain –April 17,  2020:Highlight Therapeutics, a  clinical-stagebio pharmaceutical  company developing RNA-based therapies against cancer, announces that  it has changed its name  from Bioncotech with immediate effect. The company has launched a new corporate website, www.highlighttherapeutics.com, and related rebranding.

Highlight  Therapeutics  also announced  that  clinical  trials  of  its  lead  product  candidate  BO-112  will  be classified numerically under the umbrella name Spotlight for ease of identification.

BO-112 is a best-in-class RNA-based therapy which has been demonstrated to initiate  a powerful immune response, leveraging a unique multi-target approach to turn ‘cold’ tumors ‘hot’ and therefore visible to the immune  system.It  has  the  potential  to  rescue  patients  who are resistant to current  checkpoint  inhibitor therapy, a very large market opportunity. BO-112 is currently being investigated in a range of clinical trials as  a  monotherapy and  in  combination with  checkpoint  inhibitors by Highlight Therapeutics  and  external collaborators including MSD, a subsidiary of Merck & Co., Inc, and UCLA.

Marisol Quintero, CEO of Highlight Therapeutics, commented:

“BO-112 highlights tumor cells,making them visible to the immune system.Our new identity as Highlight Therapeutics, and the branding of our expanding clinical  trial  program under  the Spotlight banner,  are  a clear representation  of  our  focus  and  the  unique approach we are taking to unlock the potential of checkpoint inhibitors in immunotherapy.

“Highlight Therapeutics has developed an extensive preclinical  package  differentiating BO-112 from other innate immune activators.  We are launching our new name at amajor inflection point in the development of  our  portfolio  as  we  work  to expand  on our initial  findings  and  apply  intratumoral  immunotherapy  to indications where we believe it has the potential to benefit many more patients, including liver metastases and melanoma.”

For more information, please contact:

Highlight Therapeutics S.L- Marisol Quintero, CEO info@highlight.com

Mo PR Advisory – Mo Noonan / Jonathan Birt Tel: +44 (0) 7876 444977/ 07860 361746

Notes to Editors

About Highlight Therapeutics

Highlight, formerly known as Bioncotech Therapeutics S.L, is a private, clinical-stage company dedicated to unlocking the full potential of immuno-oncology. Its lead drug candidate BO-112 is a best-in-class RNA-based therapy which has been demonstrated to initiate a powerful immune response, leveraging aunique multi-target approach to turn ‘cold’ tumors ‘hot’ and therefore visible to the immune system. It has the potential to rescue patients who are resistant to current checkpoint inhibitor therapy, a very large market opportunity. BO-112 is currently being investigated in a range of clinical trials as a monotherapy and in combination with checkpoint  inhibitors.  In addition to in-house  research,  Highlight  Therapeutics  has  a  numberof  external collaborators, including Merck & Co and UCLA.