Human Patient Samples and Clinical Data webinar

The FABA-US Chapter is pleased to welcome you to our monthly webinar series and we are very much looking forward to your talk on November 16th, 2024 @ 9 PM | IST. Please find attached brochure to the event, that you may share with your network and post on your company website as well. Also I am attaching herewith, the Agenda for the session.

Webinar on November 16th, @ 10.30 AM EST (or) 09.00 PM IST, on Sapien Biobank, by Jugnu Jain

Register soon to reserve your spot! Register here: https://lnkd.in/gR4c-5He

Clean Air, Healthy Lungs, Better Living!

When a person has interstitial lung disease (ILD), parts of the lungs that help oxygen get into our blood and out to our tissues are damaged. Scarring in the lungs makes it hard to breathe, and the person might develop a chronic cough. Lack of oxygen makes patients feel tired all the time.
Some causes of ILD aren’t preventable. However, one can reduce the risk of ILD by managing underlying conditions and avoiding breathing in harmful substances.
• Avoid or wear a respirator (a mask that filters particles from the air) when working around harmful substances, such as asbestos, metal dusts or chemicals.
• Avoid or wear a respirator when working around things that can cause chronic allergic reactions, like hay, grain, bird droppings or feathers and heating and cooling systems.
• Quit smoking.
Take preventive measures to reduce the risk. Clean air is essential for healthy lungs and exposure to air pollution can cause inflammation and worsening of the symptoms of ILD.
In Sapien Biobank, we have the data of 25 patients with ILD of different histology as shown below. These samples and data can enable R&D into new drug targets and biomarkers for improving the treatment of ILD patients.

Symptoms of interstitial lung disease

Interstitial lung diseases (ILD) are a group of rare lung conditions that cause chronic breathlessness. The problem usually develops over the age of 50 years. The most common symptom of all Interstitial Lung Diseases (ILDs) is shortness of breath. This is often accompanied by a dry cough, chest discomfort, fatigue and occasionally weight loss.


The global prevalence of ILD varies by region, with an estimated range of 50 to 100 cases per 100,000 population. In India, ILD prevalence studies suggest a growing burden, with around 70-100 cases per 100,000, depending on the region.
Generally, the causes of these diseases are unknown but exposure to substances like asbestos, silica, moulds, fungi or bacteria, tobacco can irritate the lungs and lead to ILD.


In most cases, by the time the symptoms appear, lung damage has already been done. So, it is important to see your doctor immediately. Severe cases that are left untreated can develop life-threatening complications including high blood pressure, heart or respiratory failure.


Let’s take a vow to adopt a healthy lifestyle because Respiratory Wellness is key to a vibrant life.

IHC staining of cancer cases @Sapien

At Sapien Biosciences, we screen our biobanked FFPE samples using Ventana IHC systems for optimization and staining of antibodies. This allows to visualize the presence and localization of target proteins within tissue samples, supporting biomarker validation, disease characterization, and therapeutic target identification. Our digital pathology capabilities include whole-slide scanning at 40X magnification for advanced AI and ML applications.


For example, IHC staining to detect MUC1 expression. MUC1 is often overexpressed or aberrantly glycosylated in many types of cancers, including breast, ovarian, lung, and pancreatic cancers. Its presence and expression levels serve as a useful biomarker for tumor detection and characterization. MUC1 is also a promising target for cancer therapeutics, including vaccine development and monoclonal antibody therapies.

Cell Assays for Immuno-Oncology R&D

June is Cancer Immunotherapy Awareness Month. Immunotherapy is a type of cancer treatment that enhances the patient’s own immune system to recognize and kill cancer cells. Several immunotherapies have been approved for use in treating cancer, such as checkpoint inhibitors, CAR-T cell therapy, and therapeutic vaccines.
The development of immuno-oncology drugs requires understanding their activity such as their ability to increase T cell response and production of cytokine. In-vitro functional assays are essential to assess their efficacy, MOA, safety and toxicity, particularly for mono- or bi-specific antibodies designed to target and kill cancer cells by recruiting patient’s immune cells.
Such clinically relevant assays using human cells are used @Sapien, as 2D or 3D tumour spheroids, to test drugs alone or in combination with FDA-approved drugs such as Keytruda, in lung cancer or triple negative breast cancer cells. The left side graph below shows one such patient-derived model, where cells were co-cultured with activated PBMCs, to assess combinatorial killing effect of a client’s anti-cancer drug with the PD-1 inhibitor Keytruda.
The right side graph below shows the Dendritic cell-Mixed Lymphocyte Reaction (DC-MLR) assay. It is used to assess the immunomodulatory activity of drugs such as Cyclosporine A or Teriflunomide, or novel NCEs or NBEs, in PBMC-derived dendritic cells stimulated with superantigen SEB and co-cultured with PBMCs.

HRR testing including BRCA1/2 can guide therapy in Ovarian Cancer

Specific types of DNA damage, such as mismatches during replication, single- or double-strand DNA breaks, can result in the activation of specific signalling and repair cascades such as homologous recombination repair (HRR) in normal cells to repair the damage. However, deficiencies in these repair pathways result in the accumulation of DNA damage, genomic instability, and an increased risk of developing cancers, particularly breast and ovarian cancers. Hence, it is important to test for mutations in the repair genes including the well-known BRCA1, BRCA2, plus others such as RAD51C, RAD51D, PALB2, and ATM, to improve the selection of targeted therapies like PARP inhibitors namely Olaparib, Niraparib, Rucaparib, and Talazoparib.

To determine the potential for PARP inhibitors in Indian ovarian cancers, we have been sequencing our 1100+ ovarian cancer resection cases using a 43-gene HRR NGS panel. We have identified several cases with BRCA mutations, as well as other HRR pathogenic/likely-pathogenic mutations in ARID1A, ATR, ATM, CDK12, CHEK2, RAD51B, FANCC, and FANCE genes. In the DNA damage response signaling pathway shown below, these genes are marked with an asterisk to indicate mutations identified in our ovarian cancer samples. These oncogenic alterations may predict response to PARP inhibitors and guide the choice of therapy to improve ovarian cancer patient lives.

Histological Distribution of Sapien’s Ovarian Cancer Cases

Ovarian cancer is comprised of various tumour groups that are histologically distinct which is important to know for their treatment. The cancer may originate in one or both ovaries, as well as in the nearby fallopian tubes or peritoneum. Diverse types of ovarian cancers are categorized based on the originating cell’s name.

Epithelial ovarian carcinomas, known as cancerous epithelial tumours, are the most prevalent among ovarian cancers. The American Cancer Society states that approximately 85 to 90 percent of ovarian cancers originate from epithelial cells that encase the outer surface of the ovary. Sapien ovarian cancer data of 1445 cases also shows that 95% of cases constitute epithelial tumours while only 5% are non-epithelial tumours such as germ cell and stromal tumours. Among epithelial tumours, 55% are identified as serous, followed by endometroid, adeno, mucinous, and clear cell carcinomas. In contrast, 64% of non-epithelial tumours are germ cell tumors and 36% are stromal tumors.

BRCA1/2 testing can guide therapy in Ovarian Cancer

Homologous recombination repair (#HRR) pathway repairs double-strand DNA breaks, and its deficiency leads to Homologous recombination deficiency (#HRD), resulting in genomic instability and contributing to cancer.
HRD mutations, including #BRCA1 or #BRCA2 mutations are important actionable biomarkers in #Ovariancancer, that are sensitive to #PARP inhibitors that block the repair of #DNAdamage, such as #olaparib, #rucaparib, and #niraparib.

Patients with mutations in BRCA1/2 account for ~15% (range 7%–21%) of ovarian cancers. Several phase-III double blind, randomized trials have shown that patients with advanced ovarian cancer carrying BRCA1/2 mutations have better progression-free survival (PFS) with PARP inhibitors compared to placebo (SOLO-1 trial Olaparib, PAOLA-1 trial Olaparib + Bevacizumab, PRIMA trial Niraparib)

We sequenced 89 of our 1100+ Ovarian cancer resection cases using a 43-gene HRR #NGS panel, which identified several mutations in genes involved in HR pathway, such as TP53, BRCA1, ARID1A, BRCA2, PTEN, ATR and ATM. We identified pathogenic/likely pathogenic BRCA1/2 #missense and #truncated mutations (see figure below) that result in the loss of BRCA1/2 tumor suppressor function. These oncogenic alterations may predict response to PARP inhibitors and guide choice of therapy.

Today is World Ovarian Cancer Day

World Ovarian Cancer Day is observed on May 8th each year, to raise awareness about Ovarian Cancer, its symptoms, risk factors, and the importance of early detection and personalized treatment. Ovarian cancer is one of the most common gynecological cancers that ranks third after cervical and uterine cancer with high incidence in Asian women (9.2 per 100,000), with poor prognosis and high mortality rate.

In our biobank, we observe most ovarian cancer cases are detected at a young age with a median age of only 53 years, and in most cases cancer had already advanced and spread to both ovaries, bilateral cancer. If they had been detected earlier, they could have been cured as the cure rate for ovarian cancer is >80% if detected at early stage.

Epidemiology of ovarian cancer, June 2020
https://pdfs.semanticscholar.org/17c5/6233f2de1692f4b542db46bfec48e8090084.pdf

Assessment of DLL3 and CD3 Expression in Pediatric Tumor FFPE Samples for Potential DLL3-Targeted Immunotherapy

Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is a promising therapeutic target that is upregulated in Small Cell Lung Cancers (SCLC) and Neuroendocrine carcinomas but is not detectable in normal adult tissues. Various DLL3-specific therapies are under clinical development, including ADC rovalpituzumab tesirine (#Abbvie), bispecific TCE molecule AMG 757 (#Amgen), and CAR-T therapy AMG 119 (#Amgen), for the treatment of SCLC and neuroendocrine carcinomas.

We evaluated DLL3 expression in several tumor types, along with CD3, a marker for T-cell infiltration in tumors, to assess their potential for DLL3-targeted immunotherapeutic agents. DLL3 showed positive staining in neuroblastoma and pediatric tumors, such as Ewing’s sarcoma, osteosarcoma, rhabdoid tumors, Hodgkin’s lymphoma, rhabdomyosarcoma, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL).