IPBA

Inflection Point Biomedical Advisors

Inflection Point Biomedical Advisors provides effective strategic advice and implement hands-on, innovative projects in Precision Medicine for the pharmaceutical and diagnostics industry, investment and VC funds as well as to the EU and US governmental agencies.

IPBA is a key collaborator and vital partner of Article25 Impact Ventures.

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News Highlights – May 2022
02/06/2022

News Highlights – May 2022

There were several highlights in May about new approvals for targeted treatments, deals for companion diagnostics and updates on drug development. May 26 was the due-date for in vitro medical devices to meet criteria of the new European IVD regulation. A day circled in red by diagnostic companies undergoing product certification, since low-risk IVDs have been postponed depending on class risk: for class-D products, 2025; C, 2026; B 2027.

Also this month, a guinness-sized prospective trial on NGS by Agendia reached 10.000 of breast cancer patients enrolled in the FLEX registry for a large-scale observational study of Real World Data to discover new genomic profiles in breast cancer. In addition, Agendia demonstrated the equivalence in terms of cost-effectiveness of their decentralized NGS services, Mammaprint and Blueprint compared to local microarray analysis. Likewise, Illumina and AHN are partnering to explore predictive genetic variations by Comprehensive Genomic Profiling (CGP) in an in-house vs an external setting. In addition, BC platforms, Euformatics and Oncompass Medicine joined forces to provide an NGS-based workflow to a consortium of seven hospitals based in Europe.

As for latest updates on liquid biopsy, Delfi Diagnostics entered into a research agreement with Memorial Sloan Kettering Cancer Center to further develop its liquid biopsy platform and translating it into clinics. Moreover, Guardant Health’s liquid biopsy test service was made available to patients with solid tumors at Vall d’Hebron Institute of Oncology in Barcelona, allowing the Comprehensive Gene Profile test for the detection of actionable mutations. Lucence announced the publication of data validating its ​​LiquidHALLMARK test to detect ctDNA in the majority of cancer patients and 70% of lung cancer patients. Still on lung cancer, Qiagen launched therascreen EGFR Plus RGQ PCR Kit for the test of both activation and resistance-related mutational variants of EGFR from tissue and liquid biopsy of patients with non-small cell lung cancer (NSCLC). Finally, the CE mark was granted to SeekInClarity Cancer Treatment Response Monitoring Kit by SeekIn, a combined strategy to test mutational tumor burden (MTB) by whole-genome sequencing (sWGS) and protein analysis (PTMs) from patients’ blood samples.

The CE-mark was also secured by Precipio for its HemeScreen panel for the test of hematologic malignancies by NGS; whereas Illumina announced the addition of a new indication as companion diagnostic (CDx) to its CE-marked TruSight Oncology (TSO) Comprehensive (EU) test to select cancer patients with solid tumors who are positive for neurotrophic tyrosine receptor kinase (NTRK) gene fusions, and eligible for the treatment Bayer's Vitrakvi (larotrectinib).

This month’s regulatory provisions for drug compounds include FDA’s approved Bristol Meyer Squibb’s Opdivo (Nivolumab) in two combinations of chemotherapy, as well as Serier’s Tibsovo (ivosidenib) plus Azacitidine in patients with newly diagnosed IDH1-mutated Acute Myeloid Leukemia. In Europe, Merck’s Keytruda (pembrolizumab) was approved, combined with chemotherapy as neoadjuvant, then continued after surgery as adjuvant monotherapy in locally advanced or early-stage Triple-Negative Breast Cancer at high risk of recurrence. In addition, Keytruda received positive EU CHMP opinion as adjuvant for adult and adolescent (≥12 Years of Age) patients with stage IIB or IIC melanoma following complete resection. Parallely, Agilent’s PD-L1 IHC 22C3 pharmDx received the CE mark.

There were also remarkable investments in the field of precision oncology. MOMA Therapeutics closed a second round of financing for the development of new drug targets based on key enzymes’ conformational changes. Verastem Oncology was granted with the first “Therapeutic Accelerator Award” by the Pancreatic Cancer Network to support a Phase 1b/2 clinical trial of VS-6766, plus defactinib in patients with front-line metastatic pancreatic cancer.

Various clinical developments of targeted therapies for lung cancer this month included: Sugemalimab, an anti-PD-L1 antibody, showing favorable results as a consolidation therapy in patients with unresectable stage 3 NSCLC without disease progression after concurrent or sequential chemoradiotherapy; Oritinib, a third generation TRK inhibitor, provided a high disease control and objective response rates in the treatment of EGFR-T790M+ NSCLC patients. Camrelizumab+chemotherapy as first line therapy, improved overall survival of patients with advanced NSCLC. As for breast cancer, a refinement of the combined treatment with Bevacizumab plus hormonal therapy showed better outcomes in patients with metastatic ER+/HER2- Breast Cancer; Trodelvy (Sacituzumab govitecan-hziy) maintained clinical response regardless of patients’ HER2 expression.

If you look for a more in-depth view on precision oncology or for a better understanding of country-related healthcare features, do not hesitate to reach out to us!

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News Highlights – April 2022
02/05/2022

News Highlights – April 2022

This spring opened with a number of compelling progresses in the adoption of diagnostics, especially in Europe.

Genetron Health obtained CE Mark for its Seq-MRD for patients with B lymphocytic leukemia and multiple myeloma before and after treatment. Lunit obtained CE mark for its Lunit Scope PD-L1 TPS, an AI-based test to analyze PD-L1 expression in both tumor and inflammatory cells from whole slide images of IHC-stained tumor tissues. Paralelly, Paige earned both CE-IVD and UKCA marks for Paige Breast Lymph Node, an AI medical device software that helps pathologists detect breast cancer metastases in lymph nodes. In addition, Agilent expanded CE-IVD mark in the European Union for its PD-L1 IHC 28-8 pharmDx to identify patients with esophageal squamous cell carcinoma eligible for BMS’s Opdivo (nivolumab) plus chemotherapy or Opdivo in combination with Yervoy (ipilimumab). The CE-IVD mark was also granted for the selection of patients with muscle-invasive urothelial carcinoma (MIUC) harboring tumor cell PD-L1 expression ≥ 1% for treatment with Opdivo (nivolumab).

This month also witnessed partnerships to promote the development of new diagnostic tools and CDx: Illumina announced a long-term strategic partnership with Janssen Biotech to co-develop CDx programs based on Illumina's TruSight Oncology Comprehensive assay; AmoyDx entered into several collaborations starting with AstraZeneca to develop and commercialize in China, Japan and the European Union CDx tests covering any type of indication or biomarker, including gene mutations leading to homologous recombination repair (HRR) deficiency in patients with prostate cancer. In the EU, AmoyDx and AstraZeneca are partnering to develop CDx for BRCA gene mutations in breast cancer patients. Still AmoyDx signed two strategic cooperations: with Hutchmed to develop a CDx in China for Osimertinib/Savolitinib combined treatment in NSCLC; and with Beckman Coulter Life Sciences to develop new applications on the Biomek NGeniuS Next Generation Library Prep System, an automatic liquid handler for NGS library preparation.

Moreover, a number of agreements were signed to promote patients' access to molecular testing. NeoGenomics announced a collaboration with Eli Lilly to provide free of charge genomic testing using NeoGenomics' NeoType DNA and RNA Assay for eligible metastatic NSCLC patients. Texas Oncology will use its precision oncology clinical pathways tool to enable test ordering of Foundation Medicine’s FoundationOne Liquid CDx Liquid Biopsy Test.

As for studies on the application of NGS in diagnostics, new data were presented by Pillar Biosciences showing high accuracy of its oncoReveal Dx Lung & Colon Cancer Assay for the detection of clinically relevant variants (KRAS G12/G13, EGFR L858 and exon 19 deletion, and BRAF V600E). Likewise, Guardant Health presented new data showing a high sensitivity rate of Guardant SHIELD multi-cancer assay to detect early-stage CRC and lung cancer.

Coming to drugs’ approval, Bristol Myers Squibb’ Opdivo (nivolumab) received EMA’s authorization as adjuvant treatment for patients with muscle-invasive urothelial carcinoma at a high risk of recurrence after surgery with PD-L1 expression ≥1% in tumor cells. The same approval was granted to Opdivo (nivolumab) and Yervoy (ipilimumab) combined with chemotherapy for patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma with PD-L1 expression ≥1% in tumor cells. In addition, Astellas Pharma and Seagen received EMA’s approval for PADCEV (enfortumab vedotin) as monotherapy for locally advanced or metastatic urothelial cancer patients.

EMA also approved Merck’s Keytruda (pembrolizumab) plus chemotherapy, with or without bevacizumab, for patients with persistent, recurrent or metastatic cervical cancer with expression of PD-L1 (CPS ≥1), and as monotherapy for patients with Microsatellite Instability-High (MSI-H) or Deficient Mismatch Repair (dMMR) tumors for five different cancer types. In addition, Merck received a positive opinion from EU CHMP for Keytruda (pembrolizumab) plus chemotherapy as neoadjuvant treatment, then in continuation as monotherapy as adjuvant treatment for patients with locally advanced, or early-stage TNBC at high risk of recurrence.

In U.S, FDA granted Breakthrough Therapy Designation to Enhertu (fam-trastuzumab deruxtecan-nxki) for patients with HER2-low (IHC 1+ or IHC 2+/ISH-negative) metastatic breast cancer, and Fast Track Designation to ONC-392, a next-generation anti-CTLA-4 monoclonal antibody, for metastatic NSCLC patients. Finally, the Chinese NMPA approved tislelizumab as 2L for patients with esophageal squamous cell carcinoma.

Stay tuned for more updates on Precision Oncology and connect with us for a deeper dive on key advancements in specific countries.

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News Highlights – March 2022
01/04/2022

News Highlights – March 2022

This month confirms a focus of companies and institutions on precision medicine to advance patients' testing and treatments, with more and more opportunities made available throughout the entire globe.

The Spanish Societies of Oncology and Pathology issued an official claim to the NHS for the coverage of biomarker testing and to establish reference centers for NGS in the National territory. FDA released new guidelines for clinical trials design including indication to speed up the approval process for cancer drugs and biologicals.

Several approvals of CDx and targeted therapies have been granted from East to West. In China, NMPA approved Burning Rock’s LungCure CDx, while in Japan, PMDA granted the approval to Guardant Health for Guardant360 CDx, a liquid biopsy test for solid tumors. EpiCheckBladder, a further LB test by Nucleix was included in this year’s clinical guidelines of the European Association of Urology (EAU) for non-muscle invasive bladder cancer (NMIBC). In the US, a milestone Rx-CDx approval was granted by FDA with Myriad’s BRACAnalysis CDx along with Astrazeneca and Merck’s Lynparza (olaparib) for the treatment of patients with early BC presenting BRCA germline mutation. In addition, FDA granted FoundationMedicine an approval for FoundationOne CDx to select patients with EGFR therapies targeting Exon 19/Exon 21 mutations in NSCLC. In addition, Guardant Health obtained local medicare coverage for its Guardant360 tissueDx.

Regarding developments in diagnostics, Illumina launched a new test for comprehensive genomic profiling in Europe. Moreover, Invitae added a new blood test in its Personalized Cancer Monitoring (PCM) platform, to detect minimal residual disease (MRD) in patients with solid tumors. Castle Bioscience’s DecisionDx®-Melanoma test showed to overcome standard T-Stage analysis in patients with cutaneous melanoma, according to an independent study.

In the field of AI and diagnostics, there have been several announcements impacting both clinics and research. Genomenon finalized a second round of financing of its gene data hub for the implementation of a broad range of AI applications for clinical decisions and research purposes. Roche will collaborate with BMS and PathAI, leveraging clinical trial settings and anatomic pathology laboratories with machine-learning solutions. Fabric Genomics announced a collaboration with MIT and Harvard to develop an AI-assisted clinical WGS system for clinical testing and reporting. Likewise, PathAI and Cleveland Clinic agreed for a 5-year partnership to implement AI solutions in translational research and routine diagnostics. Within a similar collaboration, Genomics England will apply Insitro’s AI-based algorithms to integrate histopathology analysis, genomic and clinical data.

As for clinical trials, Merk’s Keytruda (pembrolizumab) showed improvement of Distant Metastasis-Free Survival (DMFS) as adjuvant therapy in resected stage IIB and IIC melanoma. In a different study Keytruda significantly improved Disease-Free Survival (DFS) in patients with stage IB-IIIA NSCLC. Merck also announced the interruption of a phase 3 trial on Keytruda combined with lynparza (olaparib) for no outcome differences with control arm in patients with metastatic castration-resistant prostate cancer. Recent data published on NEJM showed that HER2-positive metastatic breast cancer patients previously receiving trastuzumab plus taxane, had a lower risk of progression or death from any cause with trastuzumab-deruxtecan vs trastuzumab-emtansine. Gilead Sciences ‘s Trodelvy (sacituzumab govitecan-hziy) improved progression-free survival (PFS) of patients with HR+/HER2- metastatic breast cancer who received prior endocrine therapy, CDK4/6 inhibitors and 3 to four lines of chemotherapy.

Among this month's approvals for targeted therapies, NMPA authorized Beigene’s Tislelizumab for the treatment of patients with solid tumors and high microsatellite instability or mismatch repair deficiency. In addition, FDA approved BioPharma’s Vonjo (pacritinib) for the treatment of patients with myelofibrosis and severe thrombocytopenia.

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News Highlights – February 2022
01/03/2022

News Highlights – February 2022

This February witnessed an update for the EU Parliament for the Fight Against Cancer Plan, several collaborations for CDx developments, as well as new Dx launches, especially for IVD tests for early-stage cancer.

AmoyDx partnered with Pierre Fabre to develop a CDx in China to detect BRAF mutation in tumor samples and select patients eligible for Braftovi (encorafenib) with or without Mektovi (binimetinib). Genetron Health and Hutchmed partnered to develop a CDx in China for Hutchmed’s Orpathys (savolitinib), a lung cancer TKI. In addition, Foundation Medicine announced an agreement with Eli Lilly to develop Foundation Medicine’s tissue- and blood-based assays (FoundationOneCDx and FoundationOneLiquid CDx) as CDx for Retevmo (selpercatinib) and other therapies in Loxo Oncology at Lilly’s pipeline. Foundation Medicine also received FDA approval for FoundationOneCDx as a CDx for Keytruda (pembrolizumab) to identify MSI-H in patients with solid tumors; as well as a Breakthrough Device Designation for its ctDNA monitoring assay FoundationOneTracker, to detect MRD in early-stage tumors. Paralelly, SeekIn received CE marking for its SeekInCare Cancer Detection Kit, a DNA-based blood test for early pan-cancer detection.

Also this month, the European Parliament adopted an updated framework with an allocation of 4 billion €, to strengthen Member States’ commitment in fighting cancer as well as giving indications on plans and economic dispositions. The update also highlighted the need for additional preventive measures; for making cancer diagnostics more accessible and affordable at EU level, by extending joint procurement procedures to include companion diagnostics; and for enabling a better access to cross-border health care and clinical trials, among others.

Moreover, new Dx tests were made available in Europe. Invitae launched FusionPlex Dx and LiquidPlex Dx, two NGS panels to test solid tumors in tissue and blood samples, respectively. Reveal Genomics launched in Spain its HER2DX genomic test, to predict the risk of HER2+ breast cancer recurrence and the likelihood of treatment response. Still in Europe, Ophiomics and Biocartis entered into a collaboration to commercialize HepatoPredict, a prognostic CE-marked IVD test that estimates the risk of liver cancer recurrence; while Mainz Biomed continued with its partnerships within Germany to commercialize its ColoAlert test, this time with Laboratory Mönchengladbach MVZ Dr. Stein & Kollegen. In France, Illumina partnered with the Jean Perrin Center at the Clermont-Ferrand University Hospital to assess the clinical value of CGP for late-stage cancer patients. The evidence will then be used to support precision medicine approaches within the French healthcare system.

Moreover, Cleveland Diagnostics presented a real-world study reinforcing the clinical utility of IsoPSA, a blood-based test detecting prostate-specific antigen (PSA) to assess the risk of prostate cancer; whereas Veracyte released data from Phase 3 NRG/RTOG 0126 study which validated clinical utility of its Decipher Prostate Genomic Classifier to help guide treatment selection in patients with intermediate risk of prostate cancer.

Regarding novel targeted therapies in oncology, the AEMPS in Spain approved the first european-developed CAR T-cell therapy for the treatment of acute lymphoblastic leukemia (ALL) resistant to conventional treatments in patients older than 25. In addition, the EMA approved Merck’s Tepmetko (tepotinib) as monotherapy for patients with advanced NSCLC harboring METex14 skipping alterations, whereas the Japanese MHLW approved Keytruda (pembrolizumab) plus Lenvima (lenvatinib) for radically unresectable or metastatic RCC. Merck also presented new data for Keytruda (pembrolizumab) from the Phase 3 KEYNOTE-522 trial, showing to prolong event-free survival (EFS) in patients with high-risk early-stage TNBC. In turn, Phase 3 DESTINY-Breast04 Trial on Daiichi Sankyo and AstraZeneca’s Enhertu (trastuzumab deruxtecan) improved both PFS and OS in Patients with HER2-Low metastatic BC. Finally, Phase 3 CheckMate -9ER Trial on BMS’ Opdivo (nivolumab) with cabozantinib showed sustained survival benefits and health-related quality of life (HRQoL) improvements after 2-year follow-up for 1L advanced RCC.

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News Highlights – January 2022
10/02/2022

News Highlights – January 2022

This year’s opening was flagged by several announcements on clinical application of advanced tools for molecular diagnostics as well as new deals for precision oncology.

The JP Morgan Healthcare Conference showcased major healthcare companies and their strategic plans foreseen for 2022. Illumina introduced Chemistry X, a new breakthrough technology advancing current sequencing status, and the DRAGEN platform for cfDNA, cfRNA and methylation analysis. Seer presented its new system for proteomic profiling of plasma and serum samples, while 10xGenomic is ready to launch a new kit for RNA profiling of FFPE samples. Furthermore, Guardant announced the release of Smart Liquid Biopsy, boosting current screening performance of 360 CDx by 100 folds.

Among the partnerships announced by Illumina in this venue stood out the one with Roche, with a 15-years long non-exclusive agreement to develop new CDx through Illumina’s TruSight Oncology 500. Likewise, an agreement with Bristol Squibb Myers provides for the use of this platform to develop new CDx, including MSI analysis. A further partnership involves Illumina’s MySeqDx to be applied by Agendia for expanding testing capabilities in breast cancer. In China, Amoy Diagnostics’ Pan Lung Cancer PCR panel was adopted by Takeda as a CDx for Alunbrig (brigatinib) for the treatment of ALK+ NSCLC patients.

Within the digital pathology field a milestone decision was taken by Brazil healthcare institutions adopting Agendia’s Digital MammaPrint, which provides physicians with an AI-aided algorithm for the prediction of likelihood of distant recurrences through the analysis of digitized breast cancer slides.

Moreover, a cloud-based storage system for data analysis allowed scientists from Stanford University to beat the previous Guinness World Record for the fastest sequencing of human genome, with a diagnostic rate 12% higher than average to spot unidentified mutations.

On liquid biopsy this month, CE mark was granted to the NeoGenomics’ RaDaR liquid biopsy test for MRD analysis and prediction of cancer recurrence. Lucence presented an expanded version of LiquidHALLMARK kit for cfDNA which includes cfRNA analysis, while Epic Sciences released DefineMBC, a multianalyte approach for metastatic BC patients with lack of tissue, comprising IF-based assay for HER2 and ER, WGS single-cell analysis on CTCs and NGS of cfDNA. Leiden University and the Biotech Support group validated a protein-based liquid biopsy test as a prognostic tool for cancer assessing the proteins expressed in the tumor microenvironment. Moreover, clinical evidence supporting Bluestar’s NGS test predictive value for pancreatic cancer’s blood samples was presented at the ASCO GI symposium.

As for drugs’ regulatory decisions, Pfizer’s Lorviqua (lornatinib) was approved by the EMA for the treatment of advanced ALK+ NSCLC patients. FDA granted a fast track designation to Celularity’s CYNK-101 in combination with chemotherapy, trastuzumab, and pembrolizumab for the treatment of advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma (G/GEJ). Fast track designations for BC were granted to enobosarm (Ostarine), a new AR inhibitor for AR+/ER+/HER- mBC; gedatolisib for HR+/HER2- mBC, while a supplement biologics license application (sBLA) was assigned to Enhertu (fam-trastuzumab deruxtecan-nxki), granting its priority review for the treatment of adult patients with unresectable or HER2-positive mBC. For NSCLC, a breakthrough designation was accorded to Cullinan Oncology's TAS6417 (CLN-081) for the treatment of locally advanced NSCLC patients harboring EGFR exon 20 insertion mutation, previously treated with platinum-based systemic chemotherapy. In addition, Genprex’s gene therapy REQORSA combined with pembrolizumab received fast track designation for the Treatment of NSCLC. UK NICE, after having accepted AstraZeneca’s Lynparza (olaparib) for the treatment of prostate cancer in Scotland, denied its application in England and Wales due to insufficient cost-effectiveness.

Updates on clinical trials of targeted therapies include AstraZeneca’s Tagrisso (osimertinib), showing durable response in EGFR+ NSCLC patients with CNS Metastases. Merck’s Keytruda (pembrolizumab) adjuvant treatment showed positive results on disease-free survival in patients with stage IB-IIIA NSCLC and a prolonged overall survival (OS) in patients with hepatocellular carcinoma. AstraZeneca’s Imfinzi (durvalumab) plus chemotherapy, showed an improvement in OS and progression-free survival (PFS) versus chemotherapy alone as a 1st-line treatment for patients with advanced biliary tract cancer. Primary endpoint of OS was met by BeiGene’s tislelizumab plus chemotherapy as a first-line treatment for patients with PD-L1+ unresectable or metastatic G/GEJ.

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Summary of the year 2021
17/01/2022

Summary of the year 2021

There is no doubt that in 2021 precision oncology made huge steps forward on the promise of targeted treatment, both on biomarkers as well on new therapies, especially in lung and breast cancer, with CRC as an emerging indication.

Indeed, one of the most remarkable breakthrough of the year are KRAS G12C inhibitors for NSCLC, along with different strategies to select patients by both tissue or liquid biopsy. NSCLC also had an important unmet need being addressed, with treatment targeting patients with EGFR exon 20 insertion mutations. Liquid biopsy is an important element on the expansion of new treatments, yet, it is important to keep in mind the current lab capability to ensure that patients are properly identified restrictively of setting.

Tissue-agnostic therapy saw important results, with Her2 being added to the list of alternatives together with NRTK and FGFR. The result from clinical trials shows that there will be a positive impact especially for breast cancer patients. Moreover, immunooncology saw an expansion to a broad range of indications, including NSCLC, TNBC, CRC and esophageal cancer. Despite all advances, the use of multiple assays does pose a major challenge for the adoption of testing in the different settings, which can lead to a large gap on the patient identification.

To tackle this issue, further harmonization studies were presented at ESMO this year for PD-L1, yet for some indications, concordance were suboptimal, which represent a major challenge for routine testing.

Furthermore, the upcoming IVDR implementation in the EU has risen even higher concerns on laboratory protocols and resources. To cope with the challenges also introduced by COVID, the European Commision decided on an additional 1- to 3-year transition phase (depending on the product class), giving more time for laboratories to meet the new regulatory requirements.

2021 is also an important milestone for patient access to broader diagnostics in many countries worldwide. In Japan, CGP tests for solid tumors were included into the NHI. In Germany and Sweden, reimbursement was granted for specific genetic signatures for breast cancer patients, while in Italy, a special funding was created with similar aim. In Spain, molecular diagnostics started to be covered in the region of Catalonia, while broader genetic tests were approved by the government to be incorporated in the national public system. In France, BCR-ABL was included into the formal reimbursement price list. In addition, commercial tests for MRD determination started to be locally financed by a private contractor in the US.

Moreover, public-private partnerships in countries with restricted testing capabilities such as in Argentina or in Saudi Arabia have been essential to enable equal access to biomarker testing.

Yet, more efforts must be taken to improve testing access for all patients, especially now that the landscape is moving towards an earlier and broader biomarker testing both through the use of large NGS panels in tissue and liquid biopsies, and through the incorporation of genetic signatures to guide treatments.

As you can see, there is still a long way to go, and from IPBA we are working on how to better address these issues enabling patients with access to high quality biomarker testing. Contact us to further understand how IPBA can help on your market access and diagnostic implementation strategy.

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News Highlights – December 2021
16/01/2022

News Highlights – December 2021

The closing of 2021 brought outstanding news on the accessibility of predictive diagnostics in Europe with key government decisions taken by two Member States.

In Spain, National Healthcare will incorporate predictive genetic analysis with public funding in the healthcare portfolio of common specialized care services, while Italy will establish regional Molecular Tumor Boards (MTBs) allowing the access to targeted therapies and the determination of extended genomic profiling tests in reference centers.

Regarding CDx approvals, this month included FoundationOneCDx, receiving FDA approval as a CDx for the following therapies: Pfizer’s BRAF inhibitor monotherapies Braftovi (encorafenib)/Mektovi (binimetinib) targeting BRAFV600E; and Novartis’ BRAF/MEK inhibitor Tafinlar (dabrafenib) plus Mekinist (trametinib) combo targeting BRAFV600E or V600K mutations. Thermo Fisher Scientific's Oncomine Dx Target Test was also approved by FDA as a CDx for NSCLC patients with EGFR exon20-insertion mutations for potential treatment with Janssen’s Rybrevant (amivantamab-vmjw).

Paralelly, Singular Genomics launched its G4 platform, a NGS sequencing platform for a wide range of applications including research in oncology and immunology. Mainz Biomed partnered with Ganzimmun Diagnostics to commercialize its colorectal cancer detection test ColoAlert, and Biodesix partnered with Spesana to automate the use of molecular diagnostics in clinical workflows for lung cancer, by integrating electronic ordering of Biodesix tests.

As for the liquid biopsy field, QIAGEN and Denovo Biopharma partnered to develop a blood-based CDx test to identify patients likely to respond to Denovo’s DB102TM, a new investigational cancer treatment for Diffuse Large B-Cell Lymphoma (DLBCL), whereas Freenome partnered with Siemens Healthineers for the identification of blood-based biomarkers for early diagnosis of breast cancer. In addition, Labcorp agreed to acquire Personal Genome Diagnostics (PGDx) to complement its liquid biopsy capabilities and to further expand its portfolio of NGS-based genomic profiling in oncology.

Among drugs’ regulatory decisions, Merck’s Keytruda (pembrolizumab) was approved by the FDA as adjuvant treatment for adult and pediatric (≥12 years of age) patients with stage IIB or IIC melanoma following complete resection; and was approved by the Japanese MHLW in combination with Lenvima (lenvatinib) for patients with unresectable, advanced or recurrent endometrial carcinoma that progressed after cancer chemotherapy. Janssen received EMA’s conditional marketing authorisation for Rybrevant (amivantamab) for patients with advanced NSCLC with EGFR exon 20 insertion mutations after failure of platinum-based therapy. In China, CStone Pharmaceuticals received approval from NMPA for Cejemly (sugemalimab) for advanced NSCLC as 1L treatment plus chemo.

In addition, Daiichi Sankyo’s patritumab deruxtecan was granted U.S. FDA Breakthrough Therapy Designation for the treatment of patients with metastatic or locally advanced EGFR-mutated (NSCLC) with disease progression or after 3rd-gen TKI and platinum-based therapies, while Merck’s Tepmetko (tepotinib) as monotherapy received EMA’s CHMP positive opinion for patients with advanced NSCLC with METex14 skipping alterations.

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News Highlights – November 2021
03/12/2021

News Highlights – November 2021

In this late fall the development of advanced diagnostics tests is fueled by new companies' partnerships, regulatory approvals and public funding worldwide.

In the liquid biopsy space, Burning Rock and Merck KGaA entered a CDx agreement for the MET inhibitor tepotinib in the Chinese market with the OncoCompass Target. AstraZeneca started a strategic collaboration with Saga Diagnostics to develop digital PCR assays for methylated targets in both liquid and tissue biopsies. In the UK, Guardant Health and The Royal Marsden NHS Foundation Trust have partnered to offer inhouse liquid biopsy testing. Bluestar Genomics presented data on their liquid biopsy test enabling early identification of patients with new-onset diabetes with 51.5% sensitivity and 98% specificity. Additionally, Datar Cancer Genetics received FDA breakthrough designation for its TriNetra blood test, which has demonstrated accuracy >99% for detecting early-stage breast cancer patients.

Further on the diagnostics field, Veracyte presented further clinical evidence on the use of Afirma Genomic Sequencing Classifier for reducing unnecessary surgeries in patients with indeterminate thyroid nodules. In Europe, Genetron received the CE-mark for their Health’s Onco PanScan panel and Roche launched the new cobas 5800.

On reimbursement, in the USA, Palmetto released a local coverage decision of commercial tests for MRD determination under specific criteria. Veracyte kept its momentum with the Prosigna Breast Cancer Test now reimbursed in Sweden, following a similar decision by the G-BA in Germany.

This month’s drug approvals include FDA granting Merck’s KEYTRUDA (pembrolizumab) as adjuvant therapy for patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy. In parallel, European Commission approved Roche’s Gavreto (pralsetinib) for the treatment of advanced NSCLC patients harbouring RET fusions, as well as Gilead’s Trodelvy (sacituzumab govitecan) as a 2L for treatment of metastatic TNBC. EU CHMP also recommended conditional approval for Amgen's Lumykras (sotorasib) for previously treated, advanced NSCLC patients harboring KRAS G12C mutations.

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News Highlights – October 2021
08/11/2021

News Highlights – October 2021

October was pivotal month for biomarker testing landscape, especially for EU countries due to the updates on the implementation of the upcoming IVDR, extending the transition phase to cancer diagnosis IVD products, delaying 1 to 3 years depending on the product.

ESMO updated clinical practice guidelines for metastatic breast cancer. Patients with TNBC tumor should get PD-L1 testing and HR+/HER2- should have PIK3CA tested, both patient groups should get gBRCAm and PALB2 is optional. Further assessments for MSI, TMB and NTRK should be performed when alternative treatment is available and guided by ESCAT scores. On the clinical side, the updates on the SPIRIT guidelines add further recommendations on protocols and documentation for all molecular and cellular pathology as well as digital methods.

Regarding diagnostics, this month Agilent PD-L1 IHC 28-8 pharmDx was granted CE-IVD mark for gastric and esophageal cancer, and expanded PD-L1 IHC 22C3 pharmDx indications for TNBC. In the USA, Agilent’s Ki-67 IHC MIB-1 pharmDx was approved as the CDx for Verzenio (abemaciclib). This represents the first approval for Ki-67 with a score ≥20%. GeneCentric Therapeutics and Labcorp are collaborating to develop RNA-based gene signatures analysis, while, NanoString released a new panel to support research on ADC-based treatment.

As for liquid biopsy, the Ghanese Yemaachi will work with Lucence to study actionable mutations in ctDNA samples from women with breast cancer using the LiquidHALLMARK assay. Guardant initiated the ORACLE study to predict recurrence at an early onset for 11 types of tumors with Guardant Reveal Blood Test. Inivata is partnering with Princess Margaret Cancer Centre to evaluate the clinical benefit of InVisionFirst-Lung and RaDaR liquid biopsy assays in lung cancer.

One of the largest digital pathology initiatives has started, as Institut Curie is implementing broad AI-based analysis on all their breast cancer slide repository. Furthermore, the Proscia AI platform has shown high specificity (93%) and sensitivity (91%) in a multi-center retrospective study to automatically identify melanoma samples. Meanwhile, PathAI and Roche signed an agreement to offer digital pathology solutions through Roche's uPath software. In China, Xiangya Hospital will partner with KFBIO to expand digital pathology with a Remote Pathology Diagnosis Platform, allowing the use of centralized pathology equipment and software to hospitals in different provinces. Especially important in China, as the use of digital pathology is helping to bridge the limited number of pathologists.

As for this month’s drug approvals, FDA granted Enhertu (trastuzumab deruxtecan) Breakthrough Therapy Designation for patients with HER2+ metastatic breast cancer. It also granted Genentech’s Tecentriq (atezolizumab) as adjuvant treatment for Stage II-IIIA PD-L1≥1% NSCLC as well as Merck’s Keytruda (pembrolizumab) plus chemo for a subgroup of advanced cervical carcinoma. In Europe, BMS received EMA approval for Opdivo (nivolumab) plus chemo for HER2-, PD-L1+ (CPS ≥ 5) gastric and esophageal cancers, while Merck’s Keytruda (pembrolizumab) was approved for 1L of locally recurrent unresectable or metastatic TNBC expressing PD-L1 (CPS ≥10).

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News Highlights – September 2021
05/10/2021

News Highlights – September 2021

September is a month with important milestones presented during ESMO and WCLC. Outstanding results from DESTINY trials paved the way for new therapeutic options and clinical standards based on Daiichi-Sankio’s conjugated MoAb ENHERTHU (trastuzumab-deruxtecan) for patients with lung, gastric and breast cancer. Impressive clinical outcomes also by IMFINZI in NSCLC (plus I/O) and in SCLC. Gilead also showed encouraging data for its anti-Trop2 conjugated antibody Trodelvy (sacituzumab-govitecan) for patients with PD-L1 positive TNBC as part of a phase III trial; while Ipsen’s Cabometyx (cabozantinib) produced a sustained response in patients with thyroid cancer.

ThermoFisher and AstraZeneca signed a partnership for the development of NGS-based CDx targeting a broad spectrum of therapies. Furthermore, Thermo’s Oncomine was granted 2 new CDx approvals: EGFR Exon 20 for NSCLC in association with Takeda’s Exkivity (mobocertinib) in the US and RET for NSCLC with Ely Lilli’s RET inhibitors in Japan. Illumina and Merck also signed an agreement to develop an HRD test for their PARPi therapies. The HRD solution is based on the Myriad test. An important advance also for melanoma patients with the approval in New York State for Castle Bioscience’s DecisionDx DiffDx, a gene profiling test for that can help with definitive diagnostics for samples with current uncertain malignant potential.

Data from the NADIM study presented at WCLC showed the predictive value of pre-treatment ctDNA levels for patients in a clinical trial setting. At ESMO, Guardant 360 Dx Liquid biopsy test consolidated its position as a key tool for treatment decisions in late-stage CRC and NSCLC. Lucence also shared data on the reliability to detect actionable mutations in patients with bladder cancer.

Still on diagnostics, the study from Robichaux and collaborators showed that not all EGFR mutations are the same and mutation profiles are directly associated with drug sensitivity levels of NSCLC patients, which can impact on clinical decision. Therefore, use of NGS can give extra support to clinicians on their decision, compared to qPCR. At ESMO, the harmonization study on PD-L1 assays for breast samples also showed a suboptimal correlation between the different tests, which poses some hurdles on the adoption of both assays in clinical routine.

Important updates of SPIRIT Guidelines for clinical research were made available, adding 14 items on patient specifications that should be collected in clinical trials, including information on molecular and digital pathology.

In Sweden, GMS will receive further SEK 220M funding to ensure their goal of universal access to high quality biomarker diagnostics. 

As for new targeted therapy regulatory decisions, they include Exelixis’ Cabometyx (cabozantinib) approval by FDA for patients with thyroid cancer refractory to radioactive iodine, Roche's Tecentriq recommendation by UK’s NICE for first-line PD-L1-Positive Bladder Cancer; and the positive opinion from EU CHMP for both Merck’s Keytruda (pembrolizumab) as a first-line treatment for metastatic PD-L1 CPS ≥ 10 TNBC and BMS’ Opdivo (nivolumab) for the treatment of HER2-negative, PD-L1 CPS ≥ 5 gastroesophageal adenocarcinomas. Finally, MHLW approved Padcev (enfortumab vedotin) for advanced urothelial cancer.

Last but not least, a milestone approval by FDA granted the first-in-history certification for Paige’s AI software applied to digital pathology, to assist the evaluation of tissue slides from prostate cancer patients. 

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News Highlights – July 2021
04/08/2021

News Highlights – July 2021


The month of July started with College of American Pathologists releasing an update to the CAP Cancer Protocols with updated report guidance for routinely tested biomarkers. Among the protocols with significant review are lung and head and neck biomarkers, as well as quantitative IHC reporting.

On the CDx field, Foundation Medicine got two new CDx approvals: ALK for NSCLC patients in association with Takeda’s brigatinib and MET exon 14 skipping for Novartis’ capmatinib. In Europe, Agilent’s PD-L1 IHC 22C3 pharmDx assay expanded its CE mark for identifying NSCLC patients with tumor PD-L1 expression ≥ 50% (TPS) eligible for Sanofi’s cemiplimab. To enable patient access to biomarker testing, OncoDNA, Tamkin Al-Seha Medical and Bayer also reached a partnership to provide NTRK testing for patients in Saudi Arabia. Another important program to provide free access to biomarker testing of liver cancer patients has come to life due to an agreement between Genetron and the Defang County of Guizhou in China.

Liquid biopsy also saw important new data with Agilent publishing on the validation of cfDNA analysis for detection of ALK fusions as well as monitoring emerging resistance to targeted therapies. Likewise, Tempus showed high sensitivity and specificity of its xF liquid biopsy test in a comparative study with other available tests.

Digital pathology reached a major milestone in Europe, with Ibex signing a deal with Unilabs to deploy Ibex's AI platform across 16 European countries for diagnosing cancer, and partnering with Sana Kliniken Berlin-Brandenburg to provide AI-aided pathology platforms to German hospitals.

Finally, concerning most recent drug approvals, Merk’s pembrolizumab reached 30 different different indications in the US with this month’s approvals, which included early-stage TNBC with chemo in neoadjuvant setting, locally advanced cutaneous squamous cell carcinoma in adjuvant treatment and as a third-line therapy for gastric Cancer. FDA also approved Astellas’ enfortumab vedotin-ejfv for urothelial cancer, who failed one or more lines of therapies and are ineligible for cisplatin-containing chemotherapy. In Europe, BMS' nivolumab obtained approval as adjuvant treatment for esophageal or gastroesophageal junction cancer patients with residual pathologic disease after chemoradiotherapy.

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News Highlights – June 2021
06/07/2021

News Highlights – June 2021


The beginning of this summer saw an important landmark with the WHO report on AI application in healthcare, which includes the six key principles for AI design and use: autonomy, beneficence, transparency, responsibility and accountability, equity and sustainability. The report release is aligned with recent proliferation of AI platforms for big data management and data generation as well as for implementing diagnostic analysis. Just this June FDA granted Ibex with the Breakthrough Device Designation for its AI-based platform applied to IHC image analysis; and PathAI presented a quality control system for HER2 IHC analysis based on a machine learning algorithm during ASCO 2021. Moreover, Philips has been selected as the national partner in the Netherlands for creating the infrastructure for image data exchange.

June marked important developments beyond Europe and the US. In Japan, Eiken Chemical has started a partnership with Illumina to provide IVD kits for the MiSeq Dx platform, and AmoyDx received the MHLW approval for their Pan Lung Cancer PCR Panel. In Brazil, Dasa has performed further acquisitions consolidating its position in the Northeast and diversifying its product portfolio. Additionally, recent study on the use of OncotypeDx may lead to broader adoption by the SUS, a major win for Brazilian patients. Saudi Al Borg labs might also file for an IPO, fueling its leadership for biomarker testing in the gulf region. In South Korea, VUNO is expanding its services towards digital pathology, empowered also by a partnership with Samsung. In China, the partnerships Berry Oncology with Alibaba and Natera with BGI will lead to disruptive changes in the market and will have consequences in the international landscape.

On the MRD run, Guardant, Inivata and Natera have presented strong data during ASCO. Natera has taken the spotlight with the CIRCULATE-Japan data, the ADLT status for Signatera and the agreements with FMI and BGI.

I/O field saw multiple approvals, with Infigratinib for the treatment of cholangiocarcinoma (US), tislelizumab for NSCLC and hepatocellular carcinoma (China), pembrolizumab combined with chemotherapy for esophageal cancer or HER2-negative gastroesophageal junction adenocarcinoma and nivo+ipi for the treatment of Mismatch Repair Deficient or MSI-H metastatic colorectal cancer (EU).

Regarding targeted therapies, AstraZeneca and HUTCHMED’s savolitinib was granted conditional approval by NMPA for NSCLC patients with MET exon 14 skipping alterations. FDA also granted Mirati’s adagrasib with a breakthrough designation, following Amgen’s sotorasib last month.

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News Highlights – May 2021
02/06/2021

News Highlights – May 2021


May marks an important milestone for long unmet needs for cancer patients: Amgen’s sotorasib (Lumakras), the first KRAS G12C monoclonal for advanced NSCLC, and Janssen’s amivantamab-vmjw (Rybrevant) for the treatment of NSCLC with EGFR exon 20 insertion mutations received a fast track approval by FDA . While Qiagen's Therascreen KRAS RGQ PCR is the CDx for KRAS tissue analysis, Guardant’s Guardant360 CDx is its CDx counterpart for liquid biopsy and the sole CDx to date for amivantamab-vmjw. Approvals with liquid biopsy will have a direct impact on the testing pathway in routine and reimbursement, especially in Europe and Japan.

Still on liquid biopsy, Vall d’Hebron Institute and the Leicester Cancer Research Centre have published the results from their collaborative study describing how blood ctDNA can discern cancer DNA signatures from early stage to metastasis, while Lucence is embarking on a validation study of its liquid biopsy test LiquidHALLMARK for the detection of actionable mutations in NSCLC patients.FoundationOne, has been approved as CDx for BridgeBio Pharma and Helsinn Group's infigratinib (Truseltiq) for use in locally advanced or metastatic cholangiocarcinoma with a positive FGFR2 fusion, making its second approval for the indication after Incyte’s pemigatinib (Pemazyre).

Immunotherapies also kept the momentum with multiple approvals in May, including Roche’s atezolizumab (Tecentriq, 1st line monotherapy treatment for metastatic NSCLC patients), BMS’ nivolumab (Opdivo, adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer) and Merck’s pembrolizumab (Keytruda, combo with trastuzumab and chemotherapy as first-line treatment in locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma). The latter, in addition, received NICE recommendation for metastatic MSI-high, mismatch repair-deficient colorectal cancer.

Digital platforms and the use of AI for diagnostics is seeing increasing investments, with the UK eastern Region financing the newly formed Early Diagnostic Institute to develop 5 blood tests based on machine learning algorithms for the early screening of cancer and chronic diseases. Additionally, Mindpeak’s AI-based solution for cell quantification in breast cancer received CE-mark and Quest Diagnostics and Paige have formed an alliance to provide a range of AI solutions applied to the whole patients management path: from diagnosis, through AI-assisted digital pathology, to self-care, through digital healthcare softwares.

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News Highlights – April 2021
05/05/2021

News Highlights – April 2021


April followed the trend of March, with many advances in the liquid biopsy field. At the same time, there is an increasing interest in regulating the space, as the European Commission is moving forward with its appraisal of the impact of Grail’s acquisition by Illumina on the EU market.

On the diagnostic side, France has started changes in its testing funding system, with the inclusion of BCR-ABL into the formal reimbursement list, the first molecular biomarker that transitioned from the innovation fund into the statutory insurance system. Further advancements in diagnostics include Guardant Health agreement with Daiichi Sankyo to provide Guardant360 as the CDx for the treatment of NSCLC patients with trastuzumab-deruxtecan, and the Illumina partnership with Kartos Therapeutics to develop an NGS-based TP53 CDx.

As for the regulatory outcomes in April, nivolumab (BMS) got approval for renal cell carcinoma in combination with cabozantinib (EMA), for gastric and oesophageal cancers in combination with chemotherapy (FDA), and received a positive CHMP opinion recommending approval for malignant pleural mesothelioma. While nivolumab has made the news with multiple trials, including a combination with Candel’s CAN-2409 (oncolytic viral immunotherapy) for advanced gliomas, it also saw the rejection of NICE for the combo nivo+ipi for first line NSCLC based on cost-effectiveness.

In addition, both EMA and FDA approved GSK’s dostarlimab for the treatment of advanced or recurrent endometrial cancer, with Roche’s Ventana MMR RxDx immunohistochemistry panel as its CDx (FDA).

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News Highlights – March 2021
07/04/2021

News Highlights – March 2021


March 2021 witnessed interesting developments in the landscape of precision oncology. Several companies joined forces to expand their portfolio of NGS solutions and optimize data management, including Bio-techne, Agilent and Merck, making a tender offer for the public stocks of Pandion Therapeutics.

Among this month's FDA drug approvals, Pfizer’s Lorbrena (Lornatinib) indication was extended as a first-line treatment for ALK-positive NSCLC patients, along with Ventana ALK IHC test as its CDx. In addition, Spectrum Pharmaceuticals’ poziotinib, received a fast track designation for HER2-exon-20-mutant NSCLC patients, addressing a large unmet need. Further immunotherapies received marketing approvals for breast cancer, urothelial carcinoma and renal cell cancer.

Liquid biopsy has seen a fast change in the landscape, with Guardant and FMI expanding access in different geographies and starting to redefine the testing practice.

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Centralisation in the time of pandemic
26/04/2020

Centralisation in the time of pandemic

This third article in our series, deciphering the diagnostic testing organisation in the UK, recapitulates lessons learned from local initiatives during the COVID-19 pandemic to adjust the current centralisation of tests.

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