Huang Qin Tang (YIV-906 / PHY906)

What It Is

Origin / Traditional Basis

• Huang Qin Tang (sometimes called Huang-Qin Decoction) is a classical Traditional Chinese Medicine (TCM) formula with a history of use for gastrointestinal symptoms (e.g. diarrhea, nausea, vomiting) and “harmonizing” the digestive tract in TCM theory. YIV-906 (PHY906) is a modern, standardized botanical drug candidate developed from that classical formula.

Composition

The formulation consists of four herbs (or their standardized extracts):

1. Glycyrrhiza uralensis (licorice)
2. Paeonia lactiflora (white peony)
3. Scutellaria baicalensis (Baikal skullcap)
4. Ziziphus jujuba (jujube) Nature+3Frontiers+3yiviva.com+3

Rationale for Modernization

• Because herbal preparations can have high variability in composition and biological activity, the developers of YIV-906 have adopted controlled manufacturing (cGMP), standardization, and “mechanism-based quality control” (MBQC) to ensure consistency between batches and to better correlate biological activity to constituents.

Clinical / Development Status

• YIV-906 is being evaluated primarily as an adjuvant (i.e., adjunct) to conventional cancer therapies (chemo, radiation, immunotherapy) rather than as a stand-alone anticancer agent. ClinicalTrials
• For example, there is an ongoing (or planned) clinical trial combining YIV-906 + sorafenib (a targeted therapy) in patients with hepatitis B–associated advanced hepatocellular carcinoma. ClinicalTrials
• Earlier phase I / II trials have explored YIV-906 in combination with chemotherapies (e.g. irinotecan, capecitabine) in gastrointestinal cancers, with a focus on reducing GI toxicities and improving tolerability. Frontiers

How It Works (Proposed / Observed Mechanisms)

Because YIV-906 is a complex, multi-component botanical formula, its actions are multifactorial, acting at multiple targets and pathways. The following mechanisms are supported by preclinical and early clinical research (but not definitively proven in humans):

Modulation of gastrointestinal inflammation / protection of GI mucosa

• Chemotherapy (especially agents like irinotecan) often damages the intestinal epithelium, provoking inflammation, ulceration, and diarrhea. YIV-906 appears to reduce GI toxicity by inhibiting pro-inflammatory mediators (e.g. NF-κB, COX-2, iNOS) in the gut. Nature
• It may also stimulate regeneration of intestinal epithelial stem/progenitor cells via activation of Wnt signaling, thereby promoting healing and repair of the gut lining. yiviva.com
• In radiation injury models, YIV-906 has been reported to reduce GI damage and improve recovery of intestinal tissue. yiviva.com

Synergism with anticancer therapies / enhancement of therapeutic index

• In animal tumor models, YIV-906 has been shown to enhance the anti-tumor activity of diverse classes of cancer therapies (chemotherapy, radiation, targeted agents) while mitigating side effects. Frontiers
• The principle is that YIV-906 might widen the “therapeutic window” — i.e. allow cancer therapies to be more effective or tolerable. yiviva.com
• One mechanism involves modulation of the tumor immune microenvironment: in a hepatocellular carcinoma model, combining YIV-906 with an anti–PD-1 immunotherapy increased infiltration and polarization of macrophages toward the “M1-like” (anti-tumor) phenotype, reduced suppressive myeloid-derived suppressor cells (MDSCs), and increased markers of innate and adaptive immune activation. Nature
• At the molecular level, certain flavonoids in YIV-906 may modulate IDO (indoleamine 2,3-dioxygenase) activity, which is an immunosuppressive enzyme in the tumor microenvironment, thereby favoring anti-tumor immunity. Nature
• YIV-906 also appears to induce an acute inflammatory response in the tumor microenvironment (as opposed to chronic inflammation), which can help “wake up” immune recognition of tumor antigens. Nature
• In addition, YIV-906 may affect drug metabolism / absorption: it has been suggested to inhibit multi-drug resistance (MDR) proteins and certain cytochrome P450 enzymes, thereby possibly increasing the bioavailability or retention of chemotherapeutic agents. bjtcm.net

Quality control and batch consistency (Mechanism-Based Quality Control, MBQC)

• In developing YIV-906, the researchers found that mere chemical “fingerprinting” (i.e. comparing mass spectrometry peaks) was insufficient to guarantee consistent biological activity. Some commercial Huang Qin Tang batches, although chemically similar, showed little or no in vivo activity in tumor + body weight protection models. yiviva.com
• Thus they developed an MBQC platform (using e.g. 18 luciferase reporter lines and enzymatic assays) designed around the known mechanistic pathways (e.g. relevant signaling pathways) to ensure each batch performs biologically as intended. yiviva.com
• This approach helps maintain consistency of therapeutic and protective effects batch to batch. yiviva.com

Why It’s Important / Potential Value

Mitigating toxicity and improving tolerability of cancer therapy

• One of the major limitations of many chemotherapies and radiation regimens is gastrointestinal toxicity (nausea, vomiting, diarrhea, mucositis). If YIV-906 can reliably lessen those adverse effects, patients may better tolerate full doses of therapy, avoid dose reductions, and maintain better quality of life.

Enhancing anticancer efficacy

• By modulating the tumor immune microenvironment and supporting synergy with immunotherapies or chemotherapies, YIV-906 may help therapies “work better” without additional toxicity. This could allow lower doses, greater responses, or extension into resistant settings.

Bridging traditional and modern medicine

• YIV-906 is often presented as a model for how a traditional herbal formula can be modernized, standardized, and integrated into an evidence-based oncology framework. Its development illustrates how to combine TCM concepts with rigorous mechanistic, pharmacological, and clinical approaches.

Expanding options in difficult cancers

• Some cancers, such as hepatocellular carcinoma, pancreatic cancer, or GI cancers, have limited effective options and high toxicity burden. Adjuvant strategies that add benefit without major additional harm are especially valuable in those settings.

Quality assurance in botanical drugs

• The MBQC approach (mechanism-based benchmarking) is a methodological advance in botanical drug development: instead of relying solely on chemical fingerprints, assessing biological pathway-level activity may help ensure consistent clinical effect. Frontiers

Considerations, Challenges & Caveats

Despite promising early data, there are many caveats and open questions. Here are key considerations:

Limited human evidence / trial size

• Most of the supportive data are from preclinical (animal, cell) models. Human clinical trials are relatively few, small, or early phase.
• Although some improvements in quality of life and reduced GI side effects have been reported in small trials, robust, large, randomized, controlled trials demonstrating clear survival or response benefits are lacking (or still in progress). Frontiers
• The trial designs to date have often been add-on rather than head-to-head superiority comparisons.

Complexity, multi-component nature, and mechanistic uncertainty

• Because YIV-906 contains multiple herbs with many constituents, attributing specific active compounds or pathways is challenging.
• The possibility of herb–drug interactions is higher with multi-component botanicals, especially in patients receiving many concomitant medications (chemotherapy, supportive care drugs).
• Some mechanistic proposals (e.g. effects on P450 enzymes, MDR proteins, IDO) require further validation, particularly in human cancer patients, not just preclinical models.

Batch consistency and standardization risk

• Even with MBQC, there is risk that batches may drift, or that components outside measured assays contribute important effects.
• Ensuring that each production lot has the same therapeutic activity is nontrivial, especially for botanical drugs subject to variations in raw herb sourcing, seasonal variation, cultivation, etc.

Safety, toxicity, and interactions

• While clinical trials so far have reported little to no YIV-906–related toxicity at studied doses, longer-term safety, especially in combination with potent anticancer agents, is not fully known. yiviva.com
• Because some constituents (e.g. licorice) can affect mineralocorticoid balance or have effects on kidney / electrolyte handling, monitoring is prudent in certain populations.
• Interaction with other drugs (especially those metabolized by cytochrome P450 enzymes) is a real concern; suppression or induction of drug-metabolizing enzymes or transporters could alter levels of chemotherapeutic or supportive agents.

Regulatory and clinical adoption hurdles

• Botanical drugs face more challenging regulatory pathways, especially in jurisdictions unfamiliar with TCM.
• Clinicians may be hesitant to incorporate an herb-derived adjunct without robust, definitive clinical evidence.
• Intellectual property, scaling, and commercial viability are nontrivial for complex botanical products.

Patient selection, timing, dosing, and schedule optimization

• It remains unclear which patient populations may derive the greatest benefit (type of cancer, stage, immunologic milieu).
• The optimal dose, schedule (when to start relative to chemotherapy), and duration of YIV-906 therapy are still under investigation.
• There may be a risk of “interfering” with certain therapies (e.g. dampening necessary inflammatory responses) if used inappropriately; hence, understanding context and timing is crucial.

Heterogeneity across tumors and microenvironments

• Tumors differ widely in immune phenotype, microenvironmental features, mutation burden, and sensitivity to immunomodulation. A botanical that works in one cancer type may not in another.
• Effects on microbiome may also vary, and some reported shifts in microbial populations are observed, though causal relevance remains uncertain. yiviva.com