On January 20, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported that members of its executive team will participate in a fireside chat at the B. Riley Oncology Investor Conference, which is being held virtually from January 20th to 21st (Press release, Actinium Pharmaceuticals, JAN 20, 2021, View Source [SID1234574124]). During the event, Sandesh Seth, Actinium’s Chairman and CEO, Dr. Mark Berger, Chief Medical Officer, and Dr. Dale Ludwig, Chief Scientific and Technology Officer will participate in a fireside chat discussion moderated by B. Riley analyst Justin Walsh.

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Fireside Chat Details

Event:

B. Riley Oncology Investor Conference

Participants:

Sandesh Seth, Chairman and CEO, Dr. Mark Berger, Chief Medical Officer, and Dr. Dale Ludwig, Chief Scientific and Technology Officer

Date:

Thursday, January 21st

Time:

3:30 p.m. ET

In addition, members of the executive team will be available for one-on-one meetings with conference attendees. Those interested in scheduling a meeting may do so by contacting their B. Riley representative or the Company at [email protected].

On January 20, 2021 Diamyd Medical reported that (Press release, Diamyd Medical, JAN 20, 2021, View Source;ClipID=3870455 [SID1234574123])
September 1, 2020 – November 30, 2020

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Net result: MSEK 104.9 (-6.8). The increase compared to previous year is a one-off effect of corresponding MSEK 117.5 due to profit from divestment of shares in Companion Medical, Inc.
Result per share: SEK 1.5 (-0.1)
Cash flow from operating activities: MSEK -14.1 (-6.1)
Cash and cash equivalents at November 30, 2020: MSEK 173.0 (50.6)
Significant events first quarter, September 1, 2020–November 30, 2020

Diamyd Medical invested its pro rata share in NextCell Pharma’s rights issue
USD 13.8 million were received after divestment in Companion Medical
Phase IIb topline results demonstrated a significant treatment effect of Diamyd in a predefined genetic patient group covering about 40-50% of all type 1 diabetes patients
Analyses of prevention trials and intralymphatic pilot trial with the diabetes vaccine Diamyd supported a positive efficacy trend in genetically defined groups of type 1 diabetes patients
Significant events after the reporting period

Positive safety evaluation of Remygen in high dose and in combination with Alprazolam gave the go-ahead for the continuation of the ReGenerate-1 trial
Meta-analysis updated with DIAGNODE-2 results provided further support for a precision medicine approach using Diamyd
Immunological analysis of Phase IIb trial with Diamyd showed differences between genetically defined patient groups
Diamyd Medical and Critical Path Institute announced data sharing collaboration to develop advanced drug development tools in type 1 diabetes
Diamyd Medical with MainlyAI and KTH were awarded VINNOVA funding for AI driven sustainable production
An additional USD 3.2 million, related to the divestment of Companion Medical, were received

Comments by CEO Ulf Hannelius

Following the announcement of the topline results from the phase IIb trial DIAGNODE-2 with Diamyd in September 2020, we have focused on additional data analyses, manufacturing activities and regulatory activities to take Diamyd and the company to the next level.

The notion that individuals carrying certain HLA genotypes have a very high likelihood of responding to Diamyd treatment has received further support from the recently updated meta-analysis that we announced last week. The analysis now includes the data from DIAGNODE-2 and encompasses data from 627 individuals that have participated in randomized clinical trials with Diamyd.

The findings from the analysis show that the two variables that influence the clinical effect of Diamyd the most are 1) the HLA genotype and 2) the dosing regimen. This is comforting additional knowledge to what we already knew about our diabetes vaccine, as we can control for both factors when designing and conducting trials. It is also reassuring that baseline glycemic values, in other words the patient’s blood glucose and insulin dose at study start, do not seem to influence the positive effect of Diamyd.

In addition, as we announced in December, the first immunological results from DIAGNODE-2 also showed significant differences between the genetically defined patient groups. The collected genetic and immunological insights support the possibility that we may be able to truly individualize the treatment through tailored trials and using real world data.

I am pleased to see that our other programs are advancing according to plan. For the Remygen (GABA) activities, the first ReGenerate-1 trial participants have been treated for a month with high dose Remygen and the combination of Remygen and Alprazolam, and the safety committee has given the greenlight for the trial to proceed as planned. Our manufacturing facility we are establishing in Umeå is being received very positively by the local life science community which gives us a great opportunity to find top talent to join our company. I am also pleased with our strong cash position, which is especially due to the proceeds that we have received through the sale of Companion Medical, Inc. to Medtronic. This puts us in a good position to advance all our operations.

In parallel to the significant scientific advances, it is very promising that the JDRF, a leading global organization funding type 1 diabetes research, has launched a screening education and awareness campaign in the United States that focuses on early detection of type 1 diabetes using autoantibody screening. This may strongly support the development of preventive treatments, and with the existing safety and efficacy data from trials in both recently diagnosed and at-risk individuals I see here an area with great potential for Diamyd.

Stockholm, January 20, 2021
Ulf Hannelius, President and CEO

Significant events during the first quarter

September 1, 2020 – November 30, 2020

Diamyd Medical fully subscribed for its pro rata share in a rights issue in NextCell Pharma
The pro rata share corresponded to approximately SEK 19.3 million, which means that the book value of the holding in NextCell Pharma after the investment increases from approximately SEK 11.7 million to approximately SEK 31 million.

Diamyd Medical received USD 13.9 million in connection with divestment in Companion Medical
In connection to the acquisition of Companion Medical, Inc. by Medtronic plc., Diamyd Medical received approximately USD 13.9 million, corresponding to SEK 120 million. Depending on achievement of certain future milestones, some additional payments may be possible, and will then be communicated if they occur.

Phase IIb topline results demonstrated a significant treatment effect of Diamyd in a predefined genetic patient group covering about 40-50% of all type 1 diabetes patients
Diamyd Medical announced the topline results from the placebo-controlled Phase IIb trial DIAGNODE-2, where the diabetes vaccine Diamyd (GAD-alum) was injected directly into a lymph node in individuals with recently diagnosed type 1 diabetes. In line with previous large-scale analysis of trials involving subcutaneous administration of Diamyd, the results, encompassing a total of 109 patients, showed a statistically significant effect in the predefined HLA (Human Leukocyte Antigen) group of trial participants. Specifically, the trial demonstrated a preservation of beta cell function at 15 months post-diagnosis, as measured by meal stimulated C-peptide. The primary endpoint, defined as meal stimulated C-peptide in the entire trial population was not met. No related severe adverse events were observed in the trial. Based on these results, Diamyd Medical would pursue the HLA restricted responder group in an upcoming pivotal Phase III program.

Analyses of prevention trials and intralymphatic pilot trial with the diabetes vaccine Diamyd supported a positive trend in genetically defined groups of type 1 diabetes patients
A combined analysis of two previous clinical prevention trials, DiAPREV-IT 1 and 2 in healthy children at high risk of type 1 diabetes, as well as additional insights from the open label pilot trial DIAGNODE-1 in children and young adults newly diagnosed with type 1 diabetes, while not reaching statistical significance, were consistent with the recently published large-scale responder analysis which showed a highly significant and clinically relevant effect of the diabetes vaccine Diamyd in individuals positive for genotypes that include HLA DR3-DQ2.

Significant events after the reporting period

Positive safety evaluation of Remygen in high dose and in combination with Alprazolam gave the go-ahead for the continuation of the trial
Following evaluation of safety data, an independent safety committee (DSMB) recommended the continuation of the investigator-initiated clinical trial ReGenerate-1, where Diamyd Medical’s GABA-based study drug Remygen is administered in combination with the GABA receptor modulator Alprazolam.

Meta-analysis updated with DIAGNODE-2 results provided further support for a precision medicine approach using Diamyd
The large scale meta-analysis, previously published in August 2020, based on data from Phase III and Phase II trials in Europe and in the United States with the type 1 diabetes vaccine Diamyd (GAD/alum), was updated with data from the European Phase IIb trial DIAGNODE-2. The meta-analysis comprises data from 627 individual patients and provided further support for a positive and statistically significant dose-dependent treatment response on the preservation of endogenous insulin production in individuals with type 1 diabetes that carry the HLA DR3-DQ2 haplotype.

Immunological analysis of Phase IIb trial with Diamyd showed differences between genetically defined patient groups
The first immunological results from DIAGNODE-2 showed that the immune response differed significantly between genetically defined patient groups for several immunological parameters following treatment with the diabetes vaccine Diamyd (GAD-alum). The results were in line with the earlier observed difference in clinical response (announced in September 2020) between individuals positive or negative for HLA type DR3-DQ2.

Diamyd Medical and Critical Path Institute announced data sharing collaboration to develop advanced drug development tools in type 1 diabetes
Diamyd Medical and the Critical Path Institute (C-Path) announced their collaboration to significantly improve the scientific community’s insight into type 1 diabetes (T1D) through Diamyd Medical’s contribution of fully anonymized data from a European Phase III trial to the Trial Outcome Measures Initiative (TOMI) T1D integrated database.

Diamyd Medical with MainlyAI and KTH were awarded VINNOVA funding for AI driven sustainable production
The project will design, test and build a sustainability framework powered by artificial intelligence (AI) for Diamyd Medical’s production facility in Umeå, Sweden.

Diamyd Medical received additional USD 3.2 million in connection with divestment of Companion Medical
A milestone was achieved in connection with the acquisition of Companion Medical, Inc. by Medtronic plc. As previous shareholder in Companion Medial, Diamyd Medical received a part of the milestone payment, approximately USD 3.2 million, corresponding to approximately SEK 28 million.

Two drugs in clinical development
Diamyd and Remygen are drugs in clinical development that focus on the underlying disease mechanisms of diabetes; the dysfunction and loss of insulin-producing beta cells in the pancreas.

Diamyd is an antigen-specific immunomodulating diabetes vaccine for the treatment and prevention of autoimmune diabetes (type 1 diabetes and LADA, Latent Autoimmune Diabetes in Adults).

Clinical data indicate the potential of the diabetes vaccine Diamyd to halt or stop the autoimmune destruction of insulin-producing beta cells. The effect is achieved by antigen-specific reprogramming of immune cells by administration of low doses of Diamyd in superficial lymph nodes. By maintaining the endogenous insulin production, Diamyd has the potential to make a significant difference in the daily life of patients as well significantly reduce the complications of type 1 diabetes. Topline results from the Phase IIb trial DIAGNODE-2 has demonstrated a significant treatment effect of Diamyd in a predefined genetic patient group.

Remygen is an oral regenerative and immunomodulatory drug candidate for the treatment of autoimmune- and type 2 diabetes. By stimulating the growth of insulin-producing cells, Remygen has the potential to reverse the disease progression in autoimmune- and type 2 diabetes. Based on clinical data, Remygen has also the potential to protect against hypoglycemia by improving the hormonal response. Remygen is now being investigated in a clinical Phase I/II trial (ReGenerate-1), where clinical efficacy is evaluated with the aim of optimizing the treatment regimen ahead of registration-based trials.

Ongoing clinical trials

Type 1 diabetes is a devastating disease which requires daily treatment with insulin to sustain life. The importance of finding a drug that improves the prospects for patients with diabetes is of utmost importance. The effect of intralymphatic administration of Diamyd, an antigen-specific immunotherapy aimed at stopping the immune system’s attack on insulin-producing beta cells in autoimmune diabetes, is evaluated in the Phase IIb trial DIAGNODE-2 and in the Phase II trial GADinLADA.

Remygen, which aims to stimulate the growth of beta cells in patients with diabetes, is evaluated in patients in a Phase I/II trial.

Trials with Diamyd in lymph node

DIAGNODE -2 – DIAMYD IN LYMPH NODES WITH ORAL SUPPLEMENTATION OF VITAMIN D
A follow-up double-blind randomized clinical trial where Diamyd is administered directly into a lymph node with oral supplements of vitamin D. The trial encompasses 109 patients from Sweden, the Czech Republic, Spain and the Netherlands, aged 12–24 years who have recently been diagnosed with type 1 diabetes. The 15-month results were presented on September 14, 2020, demonstrating a significant treatment effect of Diamyd in a predefined patient group. As of autumn 2019, patients who had not yet completed their last visit at 15 months were offered to participate in an extension of the trial for another 9 months. 53 patients agreed to participate in the extension trial and 15 of these patients have already been followed for 24 months. Results of this extended trial should be available in Q3 2021. Coordinating Investigator is Professor Johnny Ludvigsson at Linköping University, Sweden. Diamyd Medical is the Sponsor of the trial.

GADinLADA – DIAMYD IN LYMPH NODES WITH ORAL SUPPLEMENTATION OF VITAMIN D
An open-label, investigator initiated clinical trial where Diamyd is administered directly into a lymph node with oral supplements of vitamin D. The trial, conducted in Norway and in Sweden, encompasses 15 patients aged 30-70 years diagnosed with LADA (Latent Autoimmune Diabetes in Adults) and not yet on inulin treatment. The aim with the trial is to evaluate the safety of intralymphatic treatment with Diamyd in LADA patients and to continuously evaluate the immunological and clinical response during a one-year period. Sponsor of the trial is the Norwegian University of Science and Technology with Ingrid K Hals as sponsor representative.

Trial with Remygen (GABA)

REGENERATE-1 – REMYGEN /ALPRAZOLAM
An open-label, investigator initiated clinical trial with Remygen. The trial includes approximately 36 patients aged 18-50 who have had type 1 diabetes for more than five years with low to non-existing insulin production. Safety and initial efficacy results from the dose escalation section of the trial have paved the way to initiate the main trial and have also demonstrated a potential effect of Remygen to improve the hormonal response to hypoglycemia. The main trial evaluates whether the insulin-producing cells can be regenerated and if the hormonal response to hypoglycaemia can be improved using Remygen and the combination of Remygen and Alprazolam. The trial is led by Professor Per-Ola Carlsson at Uppsala University, Sponsor of the trial.

Manufacturing of GAD65 in Umeå
A new facility for vaccine manufacturing is being set up in Umeå, the Capital of Västerbotten County in Sweden, for the manufacture of recombinant GAD65, the active pharmaceutical ingredient in the therapeutic diabetes vaccine Diamyd currently in late-stage clinical development. The 10 000 square feet site, comprising of clean rooms, laboratory facilities and office space, will facilitate full control, predictability and scalability of the manufacturing technology of the active ingredient.

On January 20, 2021 Inivata, a leader in liquid biopsy, reported that the first patients have been tested using InVisionFirst-Lung as part of the Phase II ALKALINE trial sponsored by the European Organisation for Research and Treatment of Cancer (EORTC) (Press release, EORTC, JAN 20, 2021, View Source [SID1234574122]). As part of the study Inivata’s InVisionFirst-Lung liquid biopsy will be used to test and monitor ALK positive non-small cell lung cancer (NSCLC) patients initiating treatment with lorlatinib, Pfizer Inc.’s third generation ALK inhibitor therapy.

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The aim of this academic trial, announced in 2019 and being supported by Pfizer, is to examine the resistance to lorlatinib in ALK positive NSCLC patients. While in the past these patients were known to respond well to ALK inhibition therapies, such as lorlatinib, drug resistance in patients has been increasing. This trial is designed to provide insights for clinicians and researchers to better understand resistance mechanisms, and to analyze the correlation between ALK resistance mutational profile and response to lorlatinib. A total of 100 patients will be involved in two study designs run in parallel across 30 participating EORTC sites across Europe.

The Phase II study is a single arm, multicenter study. InVisionFirst-Lung will be used to provide data on ALK mutational profile following progression to second generation TKI’s, prior to lorlatinib treatment. This mutational profile will be correlated with lorlatinib treatment outcome after 12 months. In addition, each patient’s response to lorlatinib treatment at the point of disease progression will be monitored using ctDNA profiling for new ALK mutations or other resistance mechanisms. This study will help clinicians to understand which patient populations are more likely to benefit from lorlatinib treatment and may also inform further treatment strategies.

InVisionFirst-Lung is also being used to provide longitudinal assessment for the sub-study selection of patients through the detection of molecular resistance at the time of disease progression to second generation TKIs. This will inform on the time of emergence of ALK and other resistance mutations and the relevance of liquid biopsy monitoring for clinical outcomes.

Clive Morris, Chief Executive Officer of Inivata, commented: "This is a positive step forward in our collaboration with the EORTC, as we work together to unlock insights which will help us improve patient treatment in cases of drug resistance, an increasing global health challenge. Inivata’s involvement in this study highlights the value of the InVision platform in optimizing patient recruitment in trials and providing rapid and repeatable genomic insights to researchers, and more broadly supports the utilization of liquid biopsy technology in clinical settings."

Laura Mezquita, MD PhD, Department of Medical Oncology, Hospital Clinic, Barcelona, and co-PI of ALKALINE trial, commented: "It is of vital importance that clinicians gain a better understanding of the patterns of resistance to drug therapies in cancer treatment, where time is of the essence in ensuring the best outcomes for patients. We hope that this study will not only provide insights on how to adjust existing treatment regimens to make them more effective for patients, but could also assist in the development of combination treatments, which would prevent this build-up of resistance in the first place."

Professor Anne-Marie Dingemans, MD PhD, Professor of Pulmonology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam and Senior PI of ALKALINE trial, said: "Using Inivata’s InVisionFirst-Lung liquid biopsy in this trial will enable us to test and closely monitor patients throughout the course of the study with high confidence in the accuracy of the data. By learning which patients are more responsive to lorlatinib, we hope that the findings of this study will be able to help clinicians to make better informed decisions for their patients."

On January 20, 2021 AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)’s reported that its Enhertu (trastuzumab deruxtecan) has been granted conditional approval in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens (Press release, AstraZeneca, JAN 20, 2021, View Source [SID1234574121]).

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In Europe, approximately 531,000 cases of breast cancer in women are diagnosed annually, with an estimated one in five cases being HER2-positive.1-3 The impact of the disease is significant, with breast cancer responsible for more than 141,000 deaths per year in Europe.1

The approval by the European Commission was based on positive results from the single-arm DESTINY-Breast01 Phase II trial, in which Enhertu showed clinically meaningful and durable antitumour activity in patients with HER2-positive metastatic breast cancer who had received two or more prior anti-HER2-based regimens.4 It follows the December 2020 recommendation for approval by the Committee for Medicinal Products for Human Use of the European Medicines Agency, which reviewed the application under its accelerated assessment procedure.

Professor Fabrice André, Head of Research, Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France, said: "One in five women with breast cancer have HER2-positive disease and those with previously treated metastatic disease often progress quickly. One of the biggest challenges in this setting has been identifying treatments that produce a durable response. The DESTINY-Breast01 trial showed a breadth, depth and durability of response not previously seen in this patient population."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "Enhertu is already transforming outcomes for patients with HER2-positive metastatic breast cancer in the US and Japan, and this approval enables us to bring the benefits of this medicine to patients in the EU. We will continue to explore the potential of Enhertu in this setting, as well as in earlier lines of treatment and stages of disease, with the ambition of improving the lives of patients with HER2-targetable breast cancer."

Gilles Gallant, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo, said: "This expedited review underscores the practice-changing potential of Enhertu for patients in the metastatic setting. Enhertu is the first-ever new medicine to be approved in breast cancer in Europe on the basis of Phase II single-arm data, and one of the fastest accelerated assessment procedures for an application in oncology."

In the DESTINY-Breast01 Phase II trial, after a median follow-up of 20.5 months, Enhertu showed a confirmed objective response rate (ORR) of 61.4%, including a 6.5% complete response rate and a 54.9% partial response rate, and an estimated median duration of response (DoR) of 20.8 months for patients with HER2-positive metastatic breast cancer who had received at least two previous lines of therapy.4

The analysis was presented during the 2020 San Antonio Breast Cancer Symposium. An earlier analysis with a median follow-up of 11.1 months was published in The New England Journal of Medicine in February 2020.5

The safety of Enhertu has been evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of Enhertu 5.4mg/kg in clinical trials. The most common adverse reactions were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anaemia, neutropenia, diarrhoea, thrombocytopenia, cough, leukopenia and headache. Cases of interstitial lung disease (ILD) or pneumonitis, were reported in 15.0% of patients, and in 2.6% of patients, ILD led to death.

Enhertu (5.4mg/kg) is approved in the US under accelerated approval, and in Japan under the conditional early approval system for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 Phase II trial. It is also approved in the US and Japan for the treatment of patients with HER2-positive unresectable advanced or recurrent gastric cancer that has progressed after a trastuzumab-containing regimen based on the DESTINY-Gastric01 Phase II trial.

Enhertu is being further assessed in several ongoing Phase III breast cancer trials as part of a broad development programme, including DESTINY-Breast02, a confirmatory trial in 3rd-line HER2-positive metastatic breast cancer, and DESTINY-Breast03, as a 2nd-line treatment. DESTINY-Breast04 is testing Enhertu in patients with metastatic breast cancer and low expression of HER2; and DESTINY-Breast05 is evaluating Enhertu as an adjuvant treatment of patients with high-risk HER2-positive early breast cancer. Additional ongoing trials are testing Enhertu in combination with other anti-cancer medicines in HER2-positive and HER2-low metastatic breast cancer.

Financial considerations
Following EU approval, an amount of $75m is due from AstraZeneca to Daiichi Sankyo as a milestone payment for HER2-positive breast cancer. In AstraZeneca, the milestones paid will be capitalised as an addition to the upfront payment made in 2019 and subsequent capitalised milestones and amortised through the profit and loss.

Sales of Enhertu in most EU territories are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertu sales in those territories as collaboration revenue in the Company’s financial statements. AstraZeneca will record product sales in respect of sales made in territories where AstraZeneca is the selling party.

For further details on the financial arrangements, please consult the collaboration agreement from March 2019.

HER2-positive breast cancer
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast cancer. HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification and is often associated with aggressive disease and a poor prognosis in breast cancer.6

There remain significant unmet clinical needs for patients with HER2-positive metastatic breast cancer. The disease remains incurable with patients eventually progressing after currently available treatment options.7,8

DESTINY-Breast01
DESTINY-Breast01 was a single-arm, open-label, global, multicentre, two-part Phase II trial testing the safety and efficacy of Enhertu in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine. The primary endpoint of the trial was ORR, as determined by independent central review. Secondary objectives included DoR, disease control rate, clinical benefit rate, progression-free survival and overall survival.

Enhertu
Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the US) is a HER2-directed antibody drug conjugate (ADC). It is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform.

ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (‘payload’) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Enhertu is comprised of a humanised anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab attached to a topoisomerase I inhibitor payload, an exatecan derivative, via by a tetrapeptide-based cleavable linker.

Development programme
A comprehensive development programme is underway globally, with nine registrational trials evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2 cancers, including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

In May 2020, Enhertu also received a Breakthrough Therapy Designation for the treatment of patients with metastatic non-small cell lung cancer whose tumours have a HER2 mutation and with disease progression on or after platinum-based therapy.

Daiichi Sankyo collaboration
Daiichi Sankyo and AstraZeneca entered a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation SERD and potential new medicine AZD9833. PARP inhibitor, Lynparza (olaparib) is a targeted treatment option for metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease state.

Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings. To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy durvalumab in combination with other oncology medicines, including Lynparza and Enhertu, assessing the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

On January 20, 2021 Nicox SA (Euronext Paris: FR0013018124, COX), an international ophthalmology company, reported a business update and financial highlights for Q4 2020 for Nicox SA and its subsidiaries (the "Nicox Group"), as well as key expected value-inflection milestones in 2021 (Press release, NicOx, JAN 20, 2021, View Source [SID1234574120]).

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Key Expected Milestones
NCX 470 first Phase 3 trial, Mont Blanc: Nicox’s lead clinical product candidate, NCX 470 is a novel nitric oxide (NO) donating prostaglandin analog. Mont Blanc is a 3-month safety and efficacy trial evaluating NCX 470 ophthalmic solution, 0.1%, against latanoprost ophthalmic solution, 0.005%, for lowering of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Top-line results are now prudently expected in H1 2022, instead of Q4 2021, given probable delays in recruitment due to COVID-19.
NCX 4251 Phase 2b trial, Mississippi: NCX 4251 is a novel patented ophthalmic suspension of fluticasone propionate nanocrystals. Mississippi is evaluating once-daily dosing NCX 4251 0.1% versus placebo for the treatment of acute exacerbations of blepharitis. Top-line results are currently expected in Q4 2021.
We expect to enter into additional agreements for ZERVIATETM (cetirizine ophthalmic solution), 0.24%, further enlarging the licensed territories and increasing potential future revenue.
Fourth Quarter 2020 and Recent Operational Highlights
Innovative pipeline

The second Phase 3 trial of NCX 470, Denali, for the lowering of IOP in patients with open-angle glaucoma or ocular hypertension, was initiated in the U.S. on November 9, 2020. Denali is a 3-month trial evaluating the safety and efficacy of NCX 470 ophthalmic solution, 0.1% versus latanoprost ophthalmic solution, 0.005% and will also include a long-term safety extension. The trial is financed jointly and in equal parts by Nicox and its Chinese partner Ocumension. Top-line results are currently expected in Q4 2022.
The Phase 2b trial of NCX 4251, Mississippi, for the treatment of acute exacerbations of blepharitis was initiated in the U.S. on December 14, 2020. Top-line results are currently expected in Q4 2021.
A Phase 3 trial of ZERVIATETM (cetirizine ophthalmic solution), 0.24%, for the treatment of ocular itching associated with allergic conjunctivitis, conducted and financed by Nicox’s Chinese partner Ocumension, was initiated in China in December 2020. This trial will support the submission of a Chinese New Drug Application.
NCX 1728 was selected as the first development candidate in a new class of agents for IOP lowering where NO-mediated effects are enhanced by concomitant action of phosphodiesterase-5 (PDE5) inhibition within the same molecule. Further optimization of the ophthalmic formulations of NCX 1728 will continue prior to initiating formal pre-Investigational New Drug (IND) tests required for the filing of an IND application.
Commercial products

The total number of prescriptions1 for VYZULTA (latanoprostene bunod ophthalmic solution), 0.024%, in the U.S. increased by 29% in the fourth quarter of 2020 compared to the fourth quarter of 2019 and by 16% compared to the third quarter of 2020 despite the challenging situation due to the COVID-19 pandemic. Along with the U.S., Canada and Argentina, VYZULTA has also been launched by Nicox’s global partner Bausch + Lomb in Mexico and was recently approved in Colombia.
ZERVIATETM (cetirizine ophthalmic solution), 0.24%, U.S. prescriptions2 increased by 56% in the fourth quarter of 2020 over the third quarter of 2020. ZERVIATE has been commercialized in the U.S. since March 2020 by Nicox’s U.S. partner Eyevance Pharmaceuticals, which was acquired in September 2020 by Santen Holdings U.S. Inc., a wholly owned subsidiary of Santen Pharmaceutical Co., Ltd of Japan, for $225 million.
Corporate

The Company completed a €15 million private placement with investors including long-term shareholder HBM Healthcare Investments alongside specialist institutional investors in the U.S. and Europe.
The European Patent Office granted a formulation patent for NCX 470, extending the European exclusivity to 2039. The equivalent U.S. patent has already been granted, and NCX 470 is also covered by granted composition of matter patents.
Fera Pharmaceuticals, Nicox’s partner for naproxcinod, will evaluate naproxcinod as a potential adjuvant treatment for patients with COVID-19 infection. Fera plans to initiate pre-clinical proof-of-concept studies in models of COVID-19 infection in early 2021.
Ora and Nicox have agreed to terminate their license agreement for the development of NCX 4280 targeting lid swelling, or morning eye congestion. All rights to NCX 4280 will return to Nicox and there are no current plans to continue the development.
We continue to closely watch the spread and impact of the COVID-19 pandemic and we will provide an update of any delays.

Fourth Quarter 2020 Financial Highlights
As of December 31, 2020, the Nicox Group had cash and cash equivalents of €47.8 million as compared with €28.0 million at December 31, 2019 and €42.2 million at September 30, 2020. Net revenue3 for the fourth quarter of 2020 was €5.8 million (consisting of €0.3 million of royalty payments and €5.5 million of license payments recognized from €14.0 million paid by Ocumension in March 2020 and initially recorded as prepaid income pursuant to accounting principles). Net revenue3 for the fourth quarter of 2019 was €0.6 million and consisted entirely of royalty payments. Net revenue3 for the full year 2020 was €8.9 million (€2.4 million in net royalties, €6.5 million in license payments), compared to €6.9 million (€2.1 million in net royalties, €4.8 million in license payments) for the full year 2019.

As of December 31, 2020, the Nicox Group had financial debt of €18.4 million in the form of a bond financing agreement with Kreos Capital signed in January 2019 and a €2 million credit agreement with Société Générale and LCL, guaranteed by the French State, and granted in August 2020 in the context of the COVID-19 pandemic.

Only the figure related to the cash position of the Nicox Group as of December 31, 2019 is audited; all other figures of this press release are non-audited.
Notes

Bloomberg data, comparing the period of the weeks ending October 2, 2020 to January 1, 2021 with the periods of the weeks ending July 3, 2020 to September 25, 2020 and October 4, 2019 to December 27, 2019
Bloomberg data, comparing the period of the weeks ending October 2, 2020 to January 1, 2021 with the period of the weeks ending July 3, 2020 to September 25, 2020
Net revenue consists of revenue from collaborations less royalty payments, which corresponds to Net profit in the consolidated statements of profit or loss