On May 4, 2022 Juniper Biologics Pte Ltd, a science-led healthcare company focused on researching, developing and commercializing novel therapies, and Helsinn Group, a fully integrated, global biopharma company with a diversified pipeline of innovative oncology assets and strong track-record of commercial execution, reported the signing of an exclusive license agreement to develop and commercialise infigratinib (INN) in Australia, New Zealand, Southeast Asia and certain markets in the Middle East and Africa (see full list below) for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (CCA) with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement (Press release, Juniper Biologics, MAY 4, 2022, View Source [SID1234615015]).

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In 2021 infigratinib obtained accelerated approval from the U.S. Food and Drug Administration (FDA) under the brand name "TRUSELTIQ" for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. This indication is based on overall response rate and duration of response. Additionally, infigratinib received conditional approval by Health Canada and provisional approval by the Therapeutics Goods Association in Australia for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement. Continued approval in the U.S., Canada and Australia for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

Infigratinib is not FDA-, Health Canada-or Therapeutics Goods Association-approved for any other indication in the United States, Canada and Australia, and is not approved for use by any other health authority.

Raman Singh, CEO of Juniper Biologics, commented: "The acquisition of infigratinib is an important addition to our oncology portfolio and a much-needed treatment for patients whose cancer has spread or cannot be removed by surgery. Our mission is to increase access to proven treatments and we trust that infigratinib will help advance the treatment of patients in markets, where there remains an unmet patient need."

Giorgio Calderari, Helsinn CEO commented: "This agreement with Juniper is another example of our Fully Integrated Targeted Therapy (FITT) Strategy in action as we continue to widen our network of partners for infigratinib. Helsinn’s renewed strategic focus is on developing highly innovative oncology assets to address unmet needs, and this license agreement with our trusted partner, Juniper Biologics, will ensure that this important treatment is accessible to patients in Australia, Southeast Asia and certain markets in Middle East and Africa." *The full list of countries covered by the license agreement includes: Algeria, Angola, Australia, Bahrain, Brunei, Cambodia, Egypt, India, Indonesia, Ivory Coast, Jordan, Kenya, Kuwait, Laos, Lebanon, Libya, Malaysia, Mauritius, Morocco, Myanmar, Nepal, New Zealand, Nigeria, Oman, Pakistan, Philippines, Qatar, Saudi Arabia, Seychelles, Singapore, South Africa, South Korea, Taiwan, Tanzania, Thailand, Tunisia, Sri Lanka, United Arab Emirates, Vietnam, Zimbabwe. About Infigratinib Infigratinib is an orally administered, selective, ATP‐competitive, kinase inhibitor of FGFR 1, 2, and 3. The therapy is currently under investigation as a potential first-line treatment for individuals with unresectable locally advanced or metastatic cholangiocarcinoma (bile duct cancer) with FGFR2 fusion/rearrangement and in the adjuvant setting for individuals with invasive urothelial carcinoma (bladder cancer) with susceptible FGFR3 genetic alterations.

About Cholangiocarcinoma (CCA) CCA represents an aggressive group of malignancies that form in the bile ducts. Although rare in most countries (with a worldwide estimated incidence of <6 per 100,000 people), the incidence of this malignancy is increasing worldwide. Because the disease is usually asymptomatic at early-stages, diagnosis may be delayed until advanced stages, when CCA typically presents as locally advanced or metastatic disease. Despite continuing advances in treatments, the prognosis for this disease remains poor, with a 5-year survival rate of <20%. FGFR2 genetic alterations are present in approximately 15% to 20% of CCA patients and represent potential targets for treatments.1,2 U.S. Indication and Important Safety Information for TRUSELTIQ (infigratinib) TRUSELTIQ (infigratinib) is indicated for the treatment of adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. Accelerated approval was granted based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s). The recommended dosage of TRUSELTIQ is 125 mg (one 100 mg capsule and one 25 mg capsule) orally once daily for 21 consecutive days followed by 7 days off therapy, in 28-day cycles. Warnings and precautions · Ocular toxicity: Retinal pigment epithelial detachment (RPED), which may cause blurred vision, occurred in 11% of 351 patients treated with TRUSELTIQ, including patients with asymptomatic RPED, with a median onset of 26 days. Perform comprehensive ophthalmological exam including optical coherence tomography prior to initiating, at 1 month, at 3 months, and then every 3 months during treatment with TRUSELTIQ. Urgently evaluate patients for onset of visual symptoms and follow up every 3 weeks until resolved or TRUSELTIQ is discontinued. Withhold TRUSELTIQ as recommended. Dry eye occurred in 29% of 351 patients; treat with ocular demulcents as needed ·

Hyperphosphatemia and soft tissue mineralization: Hyperphosphatemia, which can lead to soft tissue mineralization, cutaneous calcinosis, non-uremic calciphylaxis, vascular calcification, and myocardial calcification, occurred in 82% of 351 patients treated with TRUSELTIQ, with a median time to onset of 8 days (range 1-349); 83% of 351 patients treated with TRUSELTIQ received phosphate binders. Monitor for hyperphosphatemia throughout treatment. Initiate phosphate-lowering therapy for serum phosphate >5.5 mg/dL; withhold TRUSELTIQ and initiate phosphate-lowering therapy for serum phosphate >7.5 mg/dL; withhold, reduce the dose, or permanently discontinue TRUSELTIQ based on duration and severity of hyperphosphatemia · Embryo-fetal toxicity: TRUSELTIQ can cause fetal harm. Advise pregnant women of the potential risk to the fetus; advise females of reproductive potential and men who are partnered with women of reproductive potential to use effective contraception during treatment with TRUSELTIQ and for 1 month after the final dose. Adverse reactions · Most common adverse reactions (incidence ≥20%, all grades): nail toxicity, stomatitis, dry eye, fatigue, alopecia, palmar-plantar erythrodysesthesia syndrome, arthralgia, dysgeusia, constipation, abdominal pain, dry mouth, eyelash changes, diarrhea, dry skin, decreased appetite, blurred vision, and vomiting. · Most common laboratory abnormalities (incidence ≥20%, all grades): increased creatinine, increased phosphate, decreased phosphate, increased alkaline phosphatase, decreased hemoglobin, increased alanine aminotransferase, increased lipase, increased calcium, decreased lymphocytes, decreased sodium, increased triglycerides, increased aspartate aminotransferase (AST), increased urate, decreased platelets, decreased leukocytes, decreased albumin, increased bilirubin, and decreased potassium.

Drug interactions · CYP3A inhibitors: Avoid use with strong and moderate CYP3A inhibitors · CYP3A inducers: Avoid use with strong and moderate CYP3A inducers · Gastric acid–reducing agents: Avoid coadministration with proton pump inhibitors, histamine-2 receptor antagonists (H2RA), and locally acting antacids. If coadministration of H2RA or locally acting antacids cannot be avoided, separate TRUSELTIQ administration · H2RA: Take TRUSELTIQ 2 hours before or 10 hours after · Locally-acting antacid: Take TRUSELTIQ 2 hours before or 2 hours after Dosage and administration · Prior to initiating TRUSELTIQ: Confirm FGFR2 fusion or rearrangement; perform comprehensive ophthalmic exam including OCT; confirm negative pregnancy test in females of reproductive potential. · Starting dose: Take TRUSELTIQ orally once daily on Days 1-21 of 28-day cycles; continue treatment until disease progression or unacceptable toxicity. Take TRUSELTIQ on an empty stomach with a glass of water at least 1 hour before or 2 hours after food at approximately the same time each day. · No renal or hepatic impairment · 125 mg (one 100 mg capsule and one 25 mg capsule) · Mild and moderate renal impairment (creatinine clearance 30-89 mL/min) · 100 mg (one 100 mg capsule) · Mild hepatic impairment (total bilirubin >upper limit of normal [ULN] to 1.5 x ULN or AST > ULN) · 100 mg (one 100 mg capsule) · Moderate hepatic impairment (total bilirubin >1.5 to 3 x ULN with any AST) · 75 mg (three 25 mg capsules) · Dose modification: Consult the TRUSELTIQ full Prescribing Information for dose modifications and monitoring recommendations for RPED, hyperphosphatemia, and other Grades 3-4 adverse reactions.

On May 4, 2022 Aadi Bioscience, Inc. (Nasdaq: AADI), a biopharmaceutical company focused on developing and commercializing precision therapies for genetically-defined cancers with alterations in mTOR pathway genes, reported it has received notification of a product-specific, permanent J-code for FYARROTM (sirolimus protein-bound particles for injectable suspension) (albumin-bound) for intravenous use for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa) (Press release, Aadi Bioscience, MAY 4, 2022, View Source [SID1234614204]).

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Under the Healthcare Common Procedure Coding System (HCPCS), the J-code (J9331) will become effective on July 1, 2022.

J-codes are permanent, product-specific reimbursement codes assigned to outpatient and physician-administered "buy and bill" products under Medicare Part B and are used by commercial insurers and government payers to facilitate and standardize claims submissions and reimbursements for medications like FYARRO (also known as nab-sirolimus). When the permanent J-code goes into effect, all hospital outpatient departments, ambulatory surgery centers and physician offices in the United States will have one consistent Healthcare Common Procedure Coding System (HCPCS) code to standardize the submission and payment of FYARRO insurance claims across Medicare, Medicare Advantage, Medicaid and commercial plans.

Brendan Delaney, Chief Operating Officer of Aadi, commented, "This is a significant milestone in FYARRO’s commercial launch and will provide a streamlined and efficient reimbursement process in all outpatient treatment settings. To date, we are encouraged by the payer coverage and are dedicated to facilitating patient access to FYARRO. This step further accelerates the successful roll out of FYARRO, the first and only approved drug to treat PEComa, which was also recently added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) as the only preferred treatment regimen for malignant PEComa".

About Malignant PEComa

Advanced malignant PEComa, defined by the World Health Organization as ‘mesenchymal tumors composed of distinctive cells that show a focal association with blood-vessel walls and usually express both melanocytic and smooth muscle markers,’ are a rare subset of soft-tissue sarcomas, with an undefined cell of origin. While there is no formal epidemiology for malignant PEComa, it is estimated that there are about 100-300 new patients per year in the United States. Malignant PEComas may arise in almost any body site (typically the uterus, retroperitoneum, lung, kidney, liver, genitourinary, and gastrointestinal tract with a female predominance) and can have an aggressive clinical course including distant metastases and ultimately death. The estimated prognosis based on retrospective reports is 12-16 months. Cytotoxic chemotherapies typically used for sarcoma show minimal benefit. Malignant PEComas have been shown to frequently harbor mutations in the TSC1 and/or TSC2 genes that result in the activation of mTOR pathway making it a rational therapeutic target for this disease.

About FYARRO

FYARRO is an mTOR inhibitor indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).

Important Safety Information

Contraindication

FYARRO is contraindicated in patients with a history of severe hypersensitivity to sirolimus, other rapamycin derivatives, or albumin.

Warnings and Precautions

Stomatitis

Stomatitis, including mouth ulcers and oral mucositis, occurred in 79% of patients treated with FYARRO, including 18% Grade 3. Stomatitis was most often first reported within 8 weeks of treatment. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Myelosuppression

FYARRO can cause myelosuppression including anemia, thrombocytopenia and neutropenia. Anemia occurred in 68% of patients; 6% were Grade 3. Thrombocytopenia and neutropenia occurred in 35% of patients each. Obtain blood counts at baseline and every 2 months for the first year of treatment and every 3 months thereafter, or more frequently if clinically indicated. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Infections

FYARRO can cause infections. Infections such as urinary tract infections (UTI), upper respiratory tract infections and sinusitis occurred in 59% of patients. Grade 3 infections occurred in 12% of patients, including a single case each of a UTI, pneumonia, skin, and abdominal infections. Monitor patients for infections, including opportunistic infections. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Hypokalemia

FYARRO can cause hypokalemia. Hypokalemia occurred in 44% of patients including 12% Grade 3 events. Monitor potassium levels prior to starting FYARRO and implement potassium supplementation as medically indicated. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Hyperglycemia

FYARRO can cause hyperglycemia. Hyperglycemia occurred in 12% of patients treated with FYARRO, all of which were Grade 3 events. Monitor fasting serum glucose prior to starting FYARRO. During treatment, monitor serum glucose every 3 months in non-diabetic patients, or as clinically indicated. Monitor serum glucose more frequently in diabetic patients. Based on the severity of the adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Interstitial Lung Disease / Non-Infectious Pneumonitis

FYARRO can cause interstitial lung disease (ILD) / non-infectious pneumonitis. ILD / non-infectious pneumonitis occurred in 18% of patients treated with FYARRO, of which all were Grades 1 and 2. Based on the severity of the adverse reaction, withhold, reduce the dose, or permanently discontinue FYARRO.

Hemorrhage

FYARRO can cause serious and sometimes fatal hemorrhage. Hemorrhage occurred in 24% of patients treated with FYARRO, including Grade 3 and Grade 5 events in 2.9% of patients each. Monitor patients for signs and symptoms of hemorrhage. Based on the severity of adverse reaction, withhold, resume at reduced dose, or permanently discontinue FYARRO.

Hypersensitivity Reactions

FYARRO can cause hypersensitivity reactions. Hypersensitivity reactions, including anaphylaxis, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis have been observed with administration of the oral formulation of sirolimus. Hypersensitivity reactions including anaphylaxis have been observed with human albumin administration. Monitor patients closely for signs and symptoms of infusion reactions during and following each FYARRO infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Monitor patients for at least 2 hours after the first infusion and as clinically needed for each subsequent infusion. Reduce the rate, interrupt infusion, or permanently discontinue FYARRO based on severity and institute appropriate medical management as needed.

Embryo-Fetal Toxicity

Based on animal studies and the mechanism of action, FYARRO can cause fetal harm when administered to a pregnant woman. In animal studies, mTOR inhibitors caused embryo-fetal toxicity when administered during the period of organogenesis at maternal exposures that were equal to or less than human exposures at the recommended lowest starting dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to avoid becoming pregnant and to use effective contraception while using FYARRO and for 12 weeks after the last dose.

Male Infertility

Azoospermia or oligospermia may be observed in patients treated with FYARRO. FYARRO is an anti-proliferative drug and affects rapidly dividing cells such as germ cells.

Immunizations and Risks Associated with Live Vaccines

No studies in conjunction with immunization have been conducted with FYARRO. Immunization during FYARRO treatment may be ineffective. Update immunizations according to immunization guidelines prior to initiating FYARRO, if possible. Immunization with live vaccines is not recommended during treatment and avoid close contact with those who have received live vaccines while on FYARRO. The interval between live vaccinations and initiation of FYARRO should be in accordance with current vaccination guidelines for patients on immunosuppressive therapies.

Risk of Transmission of Infectious Agents with Human Albumin

FYARRO contains human albumin, a derivative of human blood. Human albumin carries only a remote risk of transmission of viral diseases because of effective donor screening and product manufacturing processes. A theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been associated with albumin.

Adverse Reactions

Adverse Reactions in PEComa

The most common adverse reactions (≥30%) were stomatitis in 27 (79%) patients; fatigue and rash in 23 (68%) patients each; infection in 20 (59%) patients; nausea and edema in 17 (50%) patients each; diarrhea, musculoskeletal pain and decreased weight in 16 (47%) patients each; decreased appetite in 15 (44%) patients; cough in 12 (35%) patients; and vomiting and dysgeusia in 11 (32%) patients each.

Laboratory Abnormalities in PEComa

The most common Grade 3 to 4 laboratory abnormalities (≥6%) were decreased lymphocytes in 7 (21%) patients; increased glucose and decreased potassium in 4 (12%) patients each; decreased phosphate in 3 (9%) patients; and decreased hemoglobin and increased lipase in 2 (6%) patients each.

Dosage interruptions

Dose interruptions of FYARRO due to an adverse reaction occurred in 22 (65%) patients. Adverse reactions which required dosage interruption in >5% of patients included stomatitis in 6 (18%) patients, pneumonitis in 5 (15%) patients, anemia in 3 (9%) patients, and dehydration, dermatitis acneiform, and thrombocytopenia in 2 (6%) patients each.

Dose reduction

Dose reductions of FYARRO due to an adverse reaction occurred in 12 (35%) patients. Adverse reactions which required dose reductions in > 5% of patients included stomatitis and pneumonitis in 3 (9%) patients each.

Drug Interactions

Reduce the dosage of FYARRO to 56 mg/m2 when used concomitantly with a moderate or weak cytochrome P-450 3A4 (CYP3A4) inhibitor. Avoid concomitant use with drugs that are strong CYP3A4 and/or P-glycoprotein (P-gp) inhibitors and inducers and with grapefruit and grapefruit juice.

Use in Specific Populations

Pregnancy

Based on the mechanism of action and findings in animals, FYARRO can cause fetal harm when administered to a pregnant woman. Advise females of the potential risk to a fetus and to avoid becoming pregnant while receiving FYARRO.

Lactation

Sirolimus is present in the milk of lactating rats. There is potential for serious adverse effects from sirolimus in breastfed infants based on mechanism of action. Because of the potential for serious adverse reactions in breastfed infants from FYARRO, advise women not to breastfeed during treatment with FYARRO and for 2 weeks after the last dose.

Females and Males of Reproductive Potential

FYARRO can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to starting treatment with FYARRO. Advise females of reproductive potential to use effective contraception and avoid becoming pregnant during treatment with and for at least twelve weeks after the last dose of FYARRO. Advise males with female partners of reproductive potential to use effective contraception and avoid fathering a child during treatment with FYARRO and for at least twelve weeks after the last dose of FYARRO. Although there are no data on the impact of FYARRO on fertility, based on available clinical findings with oral formulation of sirolimus and findings in animals, male and female fertility may be compromised by the treatment with FYARRO.

Pediatric

The safety and effectiveness of FYARRO in pediatric patients have not been established.

Geriatric Use

Of the 34 patients treated with FYARRO, 44% were 65 years of age and older, and 6% were 75 years of age and older. Clinical studies of FYARRO did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

Hepatic Impairment

FYARRO is not recommended for use in patients with severe hepatic impairment. Reduce FYARRO dosage in patients with mild or moderate hepatic impairment.

On May 4, 2022 Novartis reported that the European Commission (EC) has approved Kymriah (tisagenlecleucel), a CAR-T cell therapy, for the treatment of adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more lines of systemic therapy (Press release, Novartis, MAY 4, 2022, View Source [SID1234614190]). The approval follows a positive opinion in March by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and is applicable to all 27 European Union member states plus Iceland, Norway and Liechtenstein. This approval marks the third indication for Kymriah and makes it the first CAR-T cell therapy approved in the EU for these patients, which include those with r/r FL grade 1, 2 and 3A1.

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"When follicular lymphoma fails to respond to treatment or comes back, it is typically more aggressive and difficult to treat; patients often end up cycling through multiple lines of therapy with decreasing benefit," said Catherine Thieblemont, MD, PhD, Professor of Hematology in the Paris VII- University, France and Head of the Hemato-Oncology Unit of St-Louis Hospital in Paris. "The approval of Kymriah in Europe brings patients closer to a potentially definitive therapy, providing us hope for improved outcomes."

The approval is based on the global Phase II ELARA trial showing that 86% of patients who were treated with Kymriah had a response, including 69% who had a complete response (CR)1. Prolonged durable response to treatment was demonstrated with an estimated 87% of patients who achieved a CR still in response at or more than nine months after initial response1. In the trial, 94 infused patients were evaluated for efficacy with a median follow-up of approximately 21 months1.

Among 97 patients evaluable for safety, the safety profile of Kymriah was remarkable1. Cytokine release syndrome (CRS) was reported in 50% of patients after Kymriah infusion, and no Grade 3 or 4 events were reported, as defined by the Lee scale1. Neurological adverse reactions occurred in 9% of patients (1% were Grade 3 or 4) within eight weeks after Kymriah infusion1. Severe infections (Grade 3 or 4) occurred in 16% of patients1.

"With this approval, we are pleased to be able to offer this transformative therapy to more people across the globe living with this advanced blood cancer," said Marie-France Tschudin, President, Innovative Medicines International & Chief Commercial Officer, Novartis. "With long-lasting responses and a safety profile that allows for flexible administration, we are striving to rewrite cancer survival and alleviate the burden of this disease for patients and the healthcare system."

In addition to r/r FL, Kymriah is approved for the treatment of pediatric and young adult patients up to and including 25 years of age with B cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse, and adult patients with r/r diffuse large B cell lymphoma (DLBCL) after two or more lines of systemic therapy1.

About Novartis commitment to Oncology Cell Therapy
As part of the unique Novartis strategy to pursue four cancer treatment platforms – radioligand therapy, targeted therapy, immunotherapy and cell and gene therapy – we strive for cures through cell therapies in order to enable more patients to live cancer-free. We will continue to pioneer the science and invest in our manufacturing and supply chain process to further advance transformative innovation.

Novartis was the first pharmaceutical company to significantly invest in pioneering CAR-T research and initiate global CAR-T trials. Kymriah, the first approved CAR-T cell therapy, developed in collaboration with the Perelman School of Medicine at the University of Pennsylvania, is the foundation of the Novartis commitment to CAR-T cell therapy.

We have made strong progress in broadening our delivery of Kymriah, which is currently available for use in at least one indication in 30 countries and at more than 370 certified treatment centers, with clinical and real-world experience from administration to more than 6,900 patients. We continue to pioneer in cell therapy, leveraging our vast experience to develop next-generation CAR-T cell therapies. These therapies will utilize our new T-Charge platform being evaluated to expand across hematological malignancies and bring hope for a cure to patients with other cancer types.

On May 4, 2022 Cristal Therapeutics, a Dutch pharmaceutical company developing tailored nanomedicines for the treatment of cancer and other diseases with high unmet patient need, reported the publication of the results of the clinical PICCOLO study in the peer-reviewed journal, Advanced Materials1 (Press release, Cristal Therapeutics, MAY 4, 2022, View Source [SID1234614016]).

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This first-of-its-kind study2, part funded by an EU Horizon 2020 and a Health Holland grant, applied radiolabelling and PET-imaging to non-invasively track CriPec nanomedicines in patients with solid tumours over time. The data showed that a diagnostic dose of CriPec nanomedicine radiolabelled with zirconium-89 (89Zr-CPC634) was reliably predictive for the behaviour of a therapeutic dose and provides a powerful tool to non-invasively monitor the biological journey, including tumour uptake. This opens up the potential of using this approach to stratify patients without exposing them to therapeutic dose levels and thus possible side effects.

In the study, undertaken in close collaboration with researchers from Amsterdam University Medical Centre (location VUmc), radiolabelled CriPec was followed by positron emission tomography / computed tomography (PET/CT) imaging in seven patients with solid tumours. A therapeutic dose as well as a diagnostic dose were administered, and pharmacokinetics and tumour uptake were assessed for both. Extended blood residence and substantial tumour uptake were observed and were in fact found to be comparable for both dose levels. These findings are significant as they provide further evidence for the long circulation and substantial tumour uptake of CriPec nanomedicines in patients, as was previously observed in other clinical studies2,3. They further support the potential for superior therapeutic performance of CriPec nanomedicines.

In addition, the ability to monitor CriPec nanoparticles in patients also provides Cristal Therapeutics with detailed information for use in its rational design process to engineer CriPec nanomedicines for superior therapeutic performance and to stratify patients for precision medicine-based approaches.

Dr Cristianne Rijcken, PharmD PhD, founder and CSO of Cristal Therapeutics said:

"Despite the many advances in the nanomedicine field, the heterogeneity of tumours, both inter- and intra-patient, remains a major challenge. The non-invasive, diagnostic approach validated in this unique study provides valuable insight into the behaviour of CriPec nanomedicines and gives Cristal Therapeutics a powerful tool to further enhance the rational design of our nanomedicines with the goal of stratifying patients for safer, more targeted anticancer treatments in the future."

Cristal Therapeutics is progressing a robust pipeline of nanoparticle therapeutic candidates which are rationally designed to target specific tissues, cells and intracellular components throughout the body. Its strategy is to partner its technology platforms and CriPec based therapeutic products to maximise the potential for advancing new medicines in areas of high unmet need.

Representatives from Cristal Therapeutics will be attending the BIO International Convention in San Diego 13-16 June 2022 – please contact [email protected].

About the PICCOLO study

In the PICCOLO clinical study, a docetaxel-entrapping polymeric nanoparticle was radiolabelled with zirconium-89 (89Zr-CPC634) and positron emission tomography / computed tomography (PET/CT) imaging was performed in seven patients with solid tumours of various origins with two different doses of CPC634: an on-treatment (containing 60 mg m-2 docetaxel) and a diagnostic (1-2 mg docetaxel) dose (NCT03712423). Pharmacokinetic half-life for 89Zr-CPC634 was mean 97.0 ±14.4 hours on-treatment, and 62.4 ±12.9 hours for the diagnostic dose (p = 0.003). At these doses accumulation was observed in 46% and 41% of tumour lesions with a median accumulation in positive lesions 96 hours post-injection of 4.94 and 4.45%IA kg-1 (p = 0.91), respectively.

Gilead Sciences has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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