On August 2, 2022 Allarity Therapeutics, Inc. ("Allarity" or the "Company"), a clinical-stage pharmaceutical company developing novel oncology therapeutics together with drug-specific DRP companion diagnostics for personalized cancer care, reported that its Board of Directors has mandated a refocus of the Company’s oncology pipeline strategy away from development of monotherapies towards development of more promising and clinically relevant combination therapies (Press release, Allarity Therapeutics, AUG 2, 2022, View Source [SID1234617291]).

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Following a lengthy and in-depth analysis of current pipeline opportunities, clinical/commercial/ regulatory risks, development costs and timelines, expected availability of funding, and in consultation with Allarity’s senior management, its Scientific Advisory Board (SAB), and external experts, Allarity’s Board of Directors has concluded that refocusing the Company’s pipeline to development of combination therapies will accomplish the following:

Align with the ongoing shift in cancer therapy standard-of-care away from monotherapies toward combination therapies, which are increasingly driving market opportunities and which have shown dramatic increases in patient benefit.
Strengthen the Company’s ability to attract additional funding from institutional life science investors, which is necessary to support the Company’s clinical development activities and future success.
Significantly broaden the Company’s possibilities for future commercial partnering with larger pharmaceutical companies to maximize the value of its pipeline assets and DRP platform technology.
Improve the likelihood of clinical and commercial success of the Company’s pipeline assets.
The Board’s decision also takes into account feedback that the Company recently received from the U.S. Food and Drug Administration (FDA) from a Type C advisory meeting held in Q2 2022, regarding a potential Phase 3 clinical development path for dovitinib as a monotherapy third-line treatment for metastatic renal cell carcinoma (mRCC). As part of that feedback, the FDA has indicated, under its recent Project Optimus guidelines relating to new optimization of therapeutic dosing, that the Company will likely need to conduct a new dosing study for dovitinib prior to Company conducting any future Phase 3 studies that could enable the submission of a new NDA. Conducting a new dosing study for dovitinib, if required, would further delay the initiation and completion of a future Phase 3 study, and increase the cost, time, and market risks of advancing dovitinib as a monotherapy in the increasingly competitive indication of third-line mRCC. In view of those delays and increased costs/risks, the Company has determined that advancing dovitinib as a monotherapy in adults is no longer commercially viable or in the best interests of its shareholders. However, the drug will continue to be externally developed, via the partnership with OncoHeroes Biosciences, as a potential monotherapy for pediatric cancers.

As part of its new strategic pipeline focus, the Company has announced it expects to initiate enrollment in a Phase 1b/2 study of its PARP inhibitor, stenoparib, in combination with its pan-TKI, dovitinib, for the second-line or later treatment of metastatic ovarian cancer by or before Q4 2022. The Company plans to have trial sites in both the U.S. and Europe. The Company is currently evaluating other potential Phase 1b/2 studies for either stenoparib or dovitinib combined with another oncology therapeutic, including the mRCC space. Allarity’s ongoing Phase 2 studies of stenoparib, as monotherapy for ovarian cancer, and IXEMPRA, as monotherapy for metastatic breast cancer, will continue through their interim data readouts, now anticipated in Q4 2022 and Q1 2023, respectively. All pipeline development activities will continue to utilize drug-specific DRP companion diagnostics to guide patient selection and treatment.

"We are grateful for the clear guidance fromour Board on the best path our Company can take to advance our mission to improve cancer patient care by realizing the promise of truly personalized medicine," said James G. Cullem, J.D., Interim Chief Executive Officer of Allarity. "New therapeutic development is recognized as a very challenging endeavor, with constantly shifting regulatory requirements, standard-of-care improvements as new drugs come to market, and financial and market challenges.It hastherefore become increasingly difficult to advance development of monotherapies in increasingly competitive therapeutic spaces. I am confident that our strategic shift of focus and resources is the correct path forward for Allarity given the current regulatory and market realities, and will best leverage our DRP companion diagnostics to match the right patients to the cancer therapeutic from which they will most likely benefit."

Dr. Duncan Moore, Ph.D., Allarity’s Board Chairman, stated: "It is clear to our Board, following lengthy discussions with our management team, SAB, and additional key opinion leaders, that the current, and future, standard of care in cancer treatment is combination therapies, and that, increasingly, the field and market opportunities are shifting away from monotherapy approaches. In view of that key shift, and in consideration of many other market and financial factors, as well as the FDA’s new Project Optimus drug dose optimization requirements, we have determined that Allarity’s future pipeline must focus on the development of promising combination therapy approaches utilizing its current assets together with DRPcompanion diagnostics. I remain very enthusiastic about the Company’s vision, mission, and strategy, and this strategic refocus towards combination therapies, together with our core DRP technology, will give Allarity the best chance of success as well as best optimize shareholder return on investment."

On August 2, 2022 PharmaJet, a biotech company that, with their innovative needle-free technology, has developed a more effective way of administering drugs and biologics to accelerate research, commercialization and public health outcomes, reported that its partner, Scancell, will include needle-free delivery of their Phase 2 clinical study for treatment of patients with advanced melanoma (Press release, Scancell, AUG 2, 2022, View Source [SID1234617307]).

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Skin cancer is by far the most common of all cancers. Melanoma accounts for only about 1% of skin cancers but causes a large majority of skin cancer deaths. The American Cancer Society’s estimates about 100,000 new melanomas will be diagnosed in the United States in 2022 and nearly 8% of those diagnosed are expected to die from it.1

Scancell’s immunotherapy platform uses the body’s immune system to identify, attack and destroy tumors. In the Phase 1/2 clinical trial, 89% of the resected patients survived for more than 5 years following vaccination with their SCIB1 vaccine. The Phase 2 study is designed to assess whether the addition of SCIB1 treatment to pembrolizumab or ipilimumab/nivolumab results in an improvement in patient outcomes for patients with metastatic disease. The updated protocol adds needle-free injection with the PharmaJet Stratis System as Scancell believes needle-free delivery could improve patient acceptance. Scancell is also using one of PharmaJet’s WHO-prequalified Needle-free Injection Systems for delivery of two SARS-CoV-2 DNA vaccine candidates, currently being evaluated in South Africa.

Chris Cappello, President and CEO, PharmaJet, commented, "We are pleased to be partnering with Scancell as they start their Phase 2 trial with a needle-free delivery option for patients with advanced melanoma. In addition to increasing patient acceptance, our partners have published data showing superior results to electroporation, and improved immunogenicity with DNA vaccines."

On August 2, 2022 Salarius Pharmaceuticals, Inc. (NASDAQ: SLRX), a clinical-stage biopharmaceutical company developing therapies for patients with cancer in need of new treatment options, and VolitionRx Limited (NYSE American: VNRX), a multinational epigenetics company, reported the signing of a research and development collaboration to advance rapid epigenetic profiling using Volition’s Nu.Q technology to support further development of Salarius’ clinical stage drug, seclidemstat (Press release, Salarius Pharmaceuticals, AUG 2, 2022, View Source [SID1234617392]).

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Seclidemstat, a novel oral, reversible, targeted LSD1 inhibitor that affects gene expression, is currently in Phase 1/2 clinical studies for solid and hematologic cancers where LSD1 is implicated in disease progression. Nu.Q has been developed as simple, easy-to-use, cost-effective blood tests to diagnose and monitor a range of life-altering diseases including cancer in humans and animals.

"We are delighted to collaborate with Volition and believe its Nu.Q technology may provide valuable biomarker information as we seek to advance the development of seclidemstat in multiple clinical indications," commented David Arthur, Chief Executive Officer of Salarius. "Biomarkers allow for a noninvasive method for determining target engagement and potential drug activity in patients. So, this exciting research collaboration with Volition Rx Limited provides another tool to aid in the development of seclidemstat in clinic."

Gael Forterre, Chief Commercial Officer of Volition, added, "We are excited to be collaborating with Salarius as part of our Nu.Q Discover program which offers biopharma companies and academia access to our state-of-the-art assays for rapid epigenetic profiling. We are looking forward to supporting Salarius in the development and release of their groundbreaking seclidemstat therapy, to directly benefit patients with cancer."

On August 2, 2022 Fresenius reported financial results for the second quarter and first half of 2022 in line with preliminary results (Press release, Fresenius, AUG 2, 2022, View Source [SID1234617236])

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FY/22 Group guidance revised
Fresenius Medical Care’s financial performance in Q2/22 was significantly impacted by worsened labor shortages and related meaningfully increased wage inflation in the U.S. The further deterioration of the macro-economic environment resulted in accelerated non-wage inflation, particularly higher supply chain costs.
Against this backdrop and growing indications for a persistent unfavorable development of these and other factors, Fresenius Medical Care has revised its outlook for FY/22.

All other Fresenius Group segments confirm their respective outlook for FY/22 for both revenue and EBIT.

However, as a consequence of the development at Fresenius Medical Care, and despite all other Fresenius Group segments confirming their respective outlook for both revenue and EBIT, Fresenius now also revises its Group outlook for FY/22. As announced on July 27, 2022, at constant currency, the Company now anticipates Group sales1 to grow in a low-to-mid single-digit percentage range (previously: mid-single digit percentage range) and Group net income2,3 to decline in a low-to-mid single-digit percentage range (previously: increase in a low-single-digit percentage range).

Without the already closed acquisitions of Ivenix and the already completed acquisition of a majority stake in mAbxience as well as any further potential acquisitions, Fresenius expects the net debt/EBITDA4 ratio (December 31, 2021: 3.51×5) to be slightly above the top end of the self-imposed target corridor of 3.0x to 3.5x by the end of 2022.

1 FY/21 base: €37,520 million
2 Net income attributable to shareholders of Fresenius SE & Co. KGaA
3 FY/21 base: €1,867 million; before special items; FY/22: before special items
4 At LTM average exchange rates for both net debt and EBITDA; pro forma closed acquisitions/divestitures; excluding further potential acquisitions; before special items; including lease liabilities
5 At LTM average exchange rates for both net debt and EBITDA; pro forma closed acquisitions/divestitures; before special items; including lease liabilities

For a detailed overview of special items please see the reconciliation tables on pages 21-24 in the PDF.

Assumptions for guidance FY/22
Due to the meaningfully increased uncertainty and volatility related to the war in Ukraine, the ongoing impacts of the COVID-19 pandemic, and a rapidly worsening global macro-economic development, Fresenius now expects significantly more pronounced headwinds in 2022 from supply chain disruptions and cost inflation, including energy prices. Furthermore, Fresenius expects significant negative effects from ongoing labor shortages and associated wage inflation, especially at Fresenius Medical Care in the U.S.

The war in Ukraine is directly and indirectly affecting Fresenius Group operations. The direct adverse effects of the war amounted to €20 million at net income level of Fresenius Group in H1/22 and are treated as a special item. Fresenius will continue to closely monitor the potential further consequences of the war, including balance sheet valuations. The guidance does not consider a significant disruption of gas or electricity supplies in Europe.
COVID-19 will continue to impact Fresenius Group operations in 2022. An unlikely but possible significant deterioration of the situation triggering containment measures that could have a significant and direct impact on the health care sector without any appropriate compensation is not reflected in the Group’s FY/22 guidance.
Furthermore, the updated assumptions for Fresenius Medical Care’s FY/22 guidance are also fully applicable to Fresenius Group’s FY/22 guidance. All of these assumptions are subject to considerable uncertainty. The acquisitions of Ivenix and of the majority stake in mAbxience as well as any further potential acquisitions remain excluded from guidance.

Group medium-term targets
As a result of the updated expectations for FY/22, Fresenius now believes its medium-term net income1 target is no longer achievable. Fresenius had expected Group organic net income1 growth to be at the bottom end of the 5% to 9% compounded annual growth rate (CAGR) range for 2020 to 2023. At the same time, Fresenius specifies its Group organic sales growth target to reach the low-end of the targeted 4% to 7% compounded annual growth rate (CAGR) range for 2020 to 2023.

1 Net income attributable to shareholders of Fresenius SE & Co. KGaA

Cost and efficiency program
The Group’s cost and efficiency program is running according to plan and Fresenius confirms its increased savings targets provided in February 2022 of at least €150 million p.a. after tax and minority interest in 2023. For the years thereafter, a further significant increase in sustainable cost savings is expected.

Management Board change at Fresenius Medical Care
Dr. Carla Kriwet will now join Fresenius Medical Care as CEO on October 1, 2022, earlier than previously announced and Rice Powell will step down as CEO effective September 30, 2022.

3% sales increase in constant currency
Group sales increased by 8% (3% in constant currency) to €10,018 million (Q2/21: €9,246 million). Organic growth was 2%. Acquisitions/divestitures contributed net 1% to growth. Currency translation increased sales growth by 5%. Excluding estimated COVID-19 effects , Group sales growth would have been 2% to 3% in constant currency (Q2/21: 6% to 7%).

In H1/22, Group sales increased by 8% (4% in constant currency) to €19,738 million (H1/21: €18,230 million). Organic growth was 3%. Acquisitions/divestitures contributed net 1% to growth. Currency translation increased sales growth by 4%. Excluding estimated COVID-19 effects1, Group sales growth would have been 4% to 5% in constant currency (H1/21: 5% to 6%).

9% net income2,3,4 decline in constant currency
Group EBITDA before special items remained stable (-6% in constant currency) at €1,682 million (Q2/212: €1,674 million). Reported Group EBITDA was €1,528 million (Q2/21: €1,662 million).

In H1/22, Group EBITDA before special items increased by 1% (-4% in constant currency) to €3,344 million (H1/212: €3,305 million). Reported Group EBITDA was €3,123 million (H1/21: €3,290 million).

Group EBIT before special items decreased by 3% (-9% in constant currency) to €1,003 million (Q2/212: €1,033 million). The decrease was mainly driven by worsened labor shortages and related meaningfully increased wage inflation at Fresenius Medical Care in the U.S. as well as elevated material and logistic costs. The EBIT margin before special items was 10.0% (Q2/212: 11.2%). Reported Group EBIT was €845 million (Q2/21: €1,021 million).

In H1/22, Group EBIT before special items decreased by 2% (-7% in constant currency) to €2,003 million (H1/212: €2,042 million). The EBIT margin before special items was 10.1% (H1/212: 11.2%). Reported Group EBIT was €1,747 million (H1/21: €2,027 million).

1 For estimated COVID-19 effects please see table on page 19.
2 Before special items
3 Net income attributable to shareholders of Fresenius SE & Co. KGaA
4 Excluding Ivenix acquisition

For a detailed overview of special items please see the reconciliation tables on pages 21-24 in the PDF.

Group net interest before special items improved to -€116 million (Q2/21: -€121 million) mainly due to positive one-time effects despite an increased interest rate environment. Reported Group net interest also improved to -€116 million (Q2/21: -€121 million). In H1/22, Group net interest before special items improved to -€235 million (H1/211: -€258 million). Reported Group net interest also improved to -€234 million (H1/21: -€258 million).

Group tax rate before special items was 23.0% (Q2/211: 21.5%) while the reported Group tax rate was 22.6% (Q2/21: 21.3%). In H1/22, Group tax rate2 before special items was 22.9% (H1/211: 22.1%) while the reported Group tax rate was 23.1% (H1/2021: 22.0%).

Noncontrolling interests before special items were -€233 million (Q2/211: -€241 million) of which 90% were attributable to the noncontrolling interests in Fresenius Medical Care. Reported noncontrolling interests were -€181 million (Q2/21: -€237 million). In H1/22, Noncontrolling interests2 before special items were -€451 million (H1/211: -€478 million) of which 89% were attributable to the noncontrolling interests in Fresenius Medical Care. Reported noncontrolling interests were -€367 million (H1/21: -€473 million).

Group net income3 before special items decreased by 5% (-9%4 in constant currency) to €450 million (Q2/211: €475 million). The decrease was mainly driven by worsened labor shortages and related meaningfully increased wage inflation at Fresenius Medical Care in the U.S. as well as elevated material and logistic costs. Excluding estimated COVID-19 effects5, Group net income3 before special items was -16% to -12% in constant currency (Q2/21: 10% to 14%). Reported Group net income3 decreased to €383 million (Q2/21: €471 million).

In H1/22, Group net income2,3 before special items remained stable (-3%4 in constant currency) at €913 million (H1/211: €911 million). Excluding estimated COVID-19 effects5, Group net income3 before special items was -10% to -6% in constant currency (H1/21: 4% to 8%). Reported Group net income3 decreased to €796 million (H1/21: €906 million).

1 Before special items
2 Q1/22 restated following remeasurement Humacyte investment
3 Net income attributable to shareholders of Fresenius SE & Co. KGaA
4 Excluding Ivenix acquisition
5 For estimated COVID-19 effects please see table on page 19

For a detailed overview of special items please see the reconciliation tables on pages 21-24 in the PDF.

Earnings per share1 before special items decreased by 6% (-11% in constant currency) to €0.80 (Q2/21 : €0.85). Reported earnings per share1 were €0.68 (Q2/21: €0.84). In H1/22, earnings per share1,3 before special items remained stable (-4% in constant currency) at €1.63 (H1/212: €1.63). Reported earnings per share1 were €1.42 (H1/21: €1.62).

Continued investment in growth
Spending on property, plant and equipment was €419 million corresponding to 4% of sales (Q2/21: €509 million; 6% of sales). These investments served primarily for the modernization and expansion of dialysis clinics, production facilities as well as hospitals and day clinics. In H1/22, spending on property, plant and equipment was €757 million corresponding to 4% of sales (H1/21: €893 million; 5% of sales).

Total acquisition spending was €291 million (Q2/21: €491 million), mainly for the acquisition of Ivenix by Fresenius Kabi and dialysis clinics at Fresenius Medical Care. In H1/22, total acquisition spending was €453 million (H1/21: €640 million).

Cash flow development
Group operating cash flow decreased to €1,017 million (Q2/21: €1,451 million) with a margin of 10.2% (Q2/21: 15.7%), mainly driven by working capital build-up from higher raw material inventories and receivables, among others, as well as phasing effects. Free cash flow before acquisitions and dividends decreased to €581 million (Q2/21: €952 million). Free cash flow after acquisitions and dividends decreased to -€391 million (Q2/21: -€359 million).

In H1/22, Group operating cash flow decreased to €1,118 million (H1/21: €2,103 million) with a margin of 5.7% (H1/21: 11.5%). Free cash flow before acquisitions and dividends decreased to €326 million (H1/21: €1,193 million). Free cash flow after acquisitions and dividends decreased to -€794 million (H1/21: -€242 million).

Solid balance sheet structure
Group total assets increased by 6% (1% in constant currency) to €76,112 million (Dec. 31, 2021: €71,962 million) given currency translation effects and the expansion of business activities. Current assets increased by 8% (4% in constant currency) to €18,818 million (Dec. 31, 2021: €17,461 million), mainly driven by the increase of trade accounts receivables. Non-current assets increased by 5% (1% in constant currency) to €57,294 million (Dec. 31, 2021: €54,501 million).

Total shareholders’ equity increased by 9% (3% in constant currency) to €32,033 million (Dec. 31, 2021: €29,288 million). The equity ratio was 42.1% (Dec. 31, 2021: 40.7%).

Group debt increased by 4% (2% in constant currency) at €28,368 million (Dec. 31, 2021: € 27,155 million). Group net debt increased by 8% (5% in constant currency) to € 26,239 million (Dec. 31, 2021: € 24,391 million).

As of June 30, 2022, the net debt/EBITDA ratio increased to 3.72×1,2 (Dec. 31, 2021: 3.51×1,2) mainly driven by dividend payments, lower EBITDA contribution as well as acquisition spending. The net debt/EBITDA as of June 30, 2022 excluding the already closed acquisition of Ivenix was 3.681,2.

1 At LTM average exchange rates for both net debt and EBITDA; pro forma closed acquisitions/divestitures
2 Before special items

For a detailed overview of special items please see the reconciliation tables on pages 21-24 in the PDF.

Business Segments

Fresenius Medical Care (Financial data according to Fresenius Medical Care press release)
Fresenius Medical Care is the world’s largest provider of products and services for individuals with renal diseases. As of June 30, 2022, Fresenius Medical Care was treating 345,687 patients in 4,163 dialysis clinics. Along with its core business, the Renal Care Continuum, the company focuses on expanding in complementary areas and in the field of critical care.

Business development impacted by unprecedented U.S. labor market situation and worsening macroeconomic environment driving cost inflation and supply chain disruptions
Meaningful decline in COVID-19-related excess mortality
Solid support by positive exchange rates
Sales increased by 10% (1% in constant currency) to €4,757 million (Q2/21: €4,320 million). Organic growth was 0%. Currency translation increased sales growth by 9%. In H1/22, sales increased by 9% (2% in constant currency) to €9,305 million (H1/21: €8,530 million). Organic growth was 1%. Currency translation increased sales growth by 7%.

EBIT decreased by 20% (-27% in constant currency) to €341 million (Q2/21: €424 million) resulting in a margin of 7.2% (Q2/21: 9.8%). EBIT before special items, i.e., costs incurred for FME25, the impacts related to the war in Ukraine, the impact of hyperinflation in Turkey and the remeasurement effect on the fair value of the investment in Humacyte, Inc. increased by 3% (-6% in constant currency) to €445 million (Q2/21: €433 million), resulting in a margin1 of 9.4% (Q2/21: 10.0%). At constant currency, the decline was mainly due to higher labor costs as well as inflationary and supply chain cost increases. This was partially offset by Provider Relief Funding received from the U.S. government to compensate for certain COVID-19-related costs.

1 Before special items
2 Net income attributable to shareholders of Fresenius Medical Care AG & Co. KGaA

For a detailed overview of special items please see the reconciliation tables on pages 21-24 in the PDF.

In H1/22, EBIT decreased by 23% (-29% in constant currency) to €688 million (H1/21: €898 million) resulting in a margin of 7.4% (H1/21: 10.5%). EBIT before special items decreased by 6% (-13% in constant currency) to €852 million (H1/21: €910 million), resulting in a margin of 9.2% (H1/21: 10.7%).

Net income2 decreased by 33% (-39% in constant currency) to €147 million (Q2/21: €219 million). Net income2 before special items remained stable (-7% in constant currency) at €225 million (Q2/21: €225 million) mainly due to the mentioned negative effects on operating income.

In H1/22, net income2 decreased by 35% (-39% in constant currency) to €305 million (H1/21: €468 million). Net income2 before special items decreased by 10%
(-15% in constant currency) to €428 million (H1/21: €476 million).

Operating cash flow was €751 million (Q2/21: €921 million) with a margin of 15.8% (Q2/21: 21.3%). The decrease was mainly due to an unfavorable development of days sales outstanding as well as a decrease in net income2, partially offset by U.S. government relief funding. In H1/22, operating cash flow was €910 million (H1/21: €1,129 million) with a margin of 9.8% (H1/21: 13.2%).

As announced on July 27, 2022, Fresenius Medical Care expects revenue to grow at a low single digit percentage rate and net income2, to decline at around a high teens percentage range. Revenue and net income guidance are both on a constant currency basis and before special items .

Given the uncertain labor situation and macro-economic inflationary environment and the substantially reduced earnings base compared to 2020, Fresenius Medical Care does not expect today to be able to achieve the meaningfully higher compounded annual average increases that would now be needed to accomplish its 2025 targets. Against this background, Fresenius Medical Care has cut its financial targets for FY 2022 and withdrawn its 2025 targets.

On August 2, 2022 Calidi Biotherapeutics, Inc. (Calidi), a clinical-stage biotechnology company that is pioneering allogeneic cell-based platforms to revolutionize oncolytic virus therapies, reported that City of Hope has received U.S. Food and Drug Administration (FDA) authorization to proceed with a phase 1 physician-sponsored clinical trial that will use Calidi’s licensed oncolytic virotherapy platform, NSC-CRAd-S-pk7 (NeuroNova), a cutting-edge therapeutic candidate comprising tumor-tropic neural stem cells delivering an oncolytic adenovirus selectively to tumor sites in patients with recurrent high-grade glioma (Calidi’s NNV-2 program) (Press release, Calidi Biotherapeutics, AUG 2, 2022, View Source [SID1234617260]).

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The phase 1 physician-sponsored clinical trial will be an open-label, non-randomized, multicenter study. Once the phase 1 trial is funded, it will address the safety and tolerability of administering serial doses of NeuroNova in adult patients with recurrent histologically confirmed high-grade gliomas (WHO grade III or IV). Secondary endpoints will evaluate treatment efficacy, including progression-free and overall survival as well as any immune response to NeuroNova. This physician-sponsored study will be led by principal investigator Jana Portnow, M.D., Professor in City of Hope’s Department of Medical Oncology & Therapeutics Research and Co-Director of the Brain Tumor Program at City of Hope, a National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network. City of Hope is one of the largest cancer research and treatment organizations in the United States.

A previously completed phase 1 dose escalation clinical trial, in newly diagnosed glioma patients, of a single dose of NSC-CRAd-S-pk7 (NeuroNova) given as an adjunct to radiation and temozolomide (Calidi’s NNV-1 program) demonstrated that NeuroNova was well tolerated in the patient population and showed promising preliminary results of efficacy [J Fares et al, Lancet Oncology, 2021, 22(8):1103-1114].

"Worldwide, an estimated 270,000 people were diagnosed with a primary brain tumor in 2020, with a five-year survival rate of only 5%. Recurrent glioma patients have poor prognosis with a median survival of less than one year. Developing our drug candidate for this indication represents a significant milestone that will empower us to help more individuals survive this devastating disease," said Calidi Biotherapeutics CEO and Chairman of the Board Allan J. Camaisa. "As Calidi undertakes this endeavor, we are pleased to have exclusive commercialization rights to this technology and thrilled to collaborate with two scientific trailblazers who have worked together on this project for over a decade: Dr. Karen Aboody, Professor in the Department of Stem Cell Biology and Regenerative Medicine, Scientific Leader of the Neuro-oncology Disease Team at City of Hope, and Dr. Maciej (Matt) Lesniak, Chair of the Department of Neurological Surgery, at Northwestern University Feinberg School of Medicine."

"Our team at City of Hope is excited to be a part of the development of NeuroNova. Despite their potential, the first-generation oncolytic virus therapies given as free virus were not very effective — most likely due to rapid inactivation by the patient’s immune system. Our new platform uses stem cells like a ‘Trojan horse’ to shield the oncolytic viral particles from immune inactivation and deliver them to the tumor sites. This results in significantly more virus distributed at the tumor sites, inducing a greater self-amplifying anti-tumor response. This may also result in a secondary anti-tumor immune response," said City of Hope’s Dr. Karen Aboody.
"In addition to significant experience with this technology, City of Hope has a proven track record in GMP manufacturing of cell and gene therapy agents."

About NeuroNova
The NeuroNova platform, NSC-CRAd-S-pk7, is an allogeneic, "off-the-shelf" therapy comprised of an immortalized Neural Stem Cell (NSC) line loaded with an engineered oncolytic adenovirus. Upon surgical resection of a tumor, NSC-CRAd-S-pk7 is injected into the walls of the resection cavity, resulting in viral infection and destruction of any remaining tumor cells. Calidi holds an exclusive worldwide licensing agreement for patents covering the NSC-CRAd-S-pk7 technology.