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 Capital.

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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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